Atormac
Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 2485  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Search
 
  
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (916 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

 
  In this Article
 »  Abstract
 » Introduction
 »  Materials and Me...
 » Results
 » Discussion
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    Viewed2577    
    Printed49    
    Emailed0    
    PDF Downloaded88    
    Comments [Add]    
    Cited by others 2    

Recommend this journal

 


 
Table of Contents    
ORIGINAL ARTICLE
Year : 2015  |  Volume : 63  |  Issue : 2  |  Page : 190-196

Cytokines, MMP-2, and MMP-9 levels in patients with a solitary cysticercus granuloma


1 Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow, India
2 Department of Microbiology, King George Medical University, Uttar Pradesh, Lucknow, India
3 Department of Biostatistics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Uttar Pradesh, Lucknow, India
4 Department of Anaesthesia, King George Medical University, Uttar Pradesh, Lucknow, India

Date of Web Publication5-May-2015

Correspondence Address:
Dr. Ravindra Kumar Garg
Department of Neurology, King George Medical University, Uttar Pradesh, Lucknow - 226 003
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.156279

Rights and Permissions

 » Abstract 

Objectives: In patients with neurocysticercosis, perilesional inflammatory activity is thought to be responsible for seizures. This study was designed to evaluate the serum and cerebrospinal fluid (CSF) concentrations of cytokines as well as matrix metalloproteinase (MMP)-2 and MMP-9 in patients with a solitary cysticercus granuloma.
Materials and Methods: The study included 47 patients suffering from seizures in whom a solitary cysticercus granuloma was detected on a computed tomography (CT) scan. The study also included 47 control subjects. Their serum and cerebrospinal fluid (CSF) was analysed for cytokines and MMP levels. A follow-up CT was performed after 6 months.
Results: The median levels of cytokines, interleukin (IL)-1β, IL-5, IL-6, IL-10 and tissue necrosis factor (TNF)-α, MMP-2 and MMP-9 were significantly elevated, both in the serum and CSF of patients having an intracerebral solitary cysticercus granuloma, in comparison to that of controls. The follow-up CT revealed that in 27 patients, the lesions were calcified and in 5 patients, there was complete resolution of the lesions. In 15 patients, the lesions remained unchanged. Higher baseline CSF MMP-2 and TNF-α level were seen in patients with persisting lesions. Higher serum baseline MMP-2, IL-6 and a low CSF IL-10 level were seen in patients with complete resolution of the granuloma. A high baseline IL-1β level was associated with a calcified lesion. Fourteen patients had recurrence of seizures. A high baseline serum TNF-α level was independently associated with seizure recurrence (P = 0.021, OR = 1.041, CI = 1.006 to 1.078).
Conclusion: In patients with a solitary cysticercus granuloma, cytokines and matrix metalloproteinases in the CSF and serum are elevated. Different patterns of immunological changes were observed in patients following resolution or calcification of the lesion.


Keywords: Cysticercosis; epilepsy; matrix metalloproteinase; neurocysticercosis; seizures; Taenia solium


How to cite this article:
Lalla RS, Garg RK, Malhotra HS, Jain A, Verma R, Pandey CM, Singh GP, Sharma PK. Cytokines, MMP-2, and MMP-9 levels in patients with a solitary cysticercus granuloma. Neurol India 2015;63:190-6

How to cite this URL:
Lalla RS, Garg RK, Malhotra HS, Jain A, Verma R, Pandey CM, Singh GP, Sharma PK. Cytokines, MMP-2, and MMP-9 levels in patients with a solitary cysticercus granuloma. Neurol India [serial online] 2015 [cited 2019 Sep 19];63:190-6. Available from: http://www.neurologyindia.com/text.asp?2015/63/2/190/156279



 » Introduction Top


A solitary cysticercus granuloma is considered as the most frequent variety of neurocysticercosis in India and is also the most frequent neuroimaging abnormality seen in patients with new-onset seizures. A solitary cysticercus granuloma is seen on a contrast enhanced computed tomographic scan as an enhancing, ring-shaped lesion. These enhancing lesions are usually less than 20 mm in diameter and may be surrounded by varying amounts of perifocal edema. In its natural course, a solitary cysticercus granuloma frequently disappears spontaneously; recurrences of the solitary form after resolution of the initial granuloma have, however, been reported. [1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11]

In the brain parenchyma, the cysticercus larva passes through four distinct stages. In the vesicular stage, the larva is in the form of a cyst filled with clear fluid. There is an eccentric scolex as well. The vesicular cysts are viable and are not associated with any inflammatory changes in the cyst wall or the surrounding brain tissue. In the colloidal stage, inflammatory changes develop in the cyst wall and in brain tissue. The cystic fluid gets converted into a jellylike material while the cyst wall becomes thick and fibrous. Later, mineralization of the cystic fluid and degeneration of the scolex leads to evolution of the granular-nodular stage. Ultimately the cyst gets mineralized in its entirety, resulting in the calcific stage. A solitary cysticercus granuloma usually represents either the colloidal stage or the "granular-nodular" stage. [1],[2],[3],[4],[5],[6],[7],[8],[9],[10] In patients with neurocysticercosis, perilesional inflammatory activity is thought to be responsible for seizures. [5] Similar to what has been suggested with focal cerebral calcifications (presumably related to neurocysticercosis), the presence of gliosis consequent to resolution of the granuloma may lead to recurrence of seizures in patients with a solitary cysticercus granuloma. [12] The resolution of the granuloma may also be affected by the use of albendazole but its exact role and the specific duration of usage still remains controversial. [13]

The T-helper type 1 (Th-1) cytokines (like interleukin (IL)-1β, IL-6 and tissue necrosis factor (TNF)-α) response is associated with a robust immune reaction against the neurocysticercal lesions. It is, however, also responsible for host tissue damage. In contrast to this, the viable parasites induce T-helper type 2 (Th-2) regulatory cytokines like IL-10 that help in avoiding the host inflammatory response and therefore, remain asymptomatic. [14] The murine model studies have shown the role of IL-1β in increasing seizure susceptibility after a central nervous system insult. [15] Seizures per se can cause elevation of pro- as well as anti-inflammatory cytokines. [16] Matrix metalloproteinase (MMP) are the zinc dependent endopeptidases responsible for degradation of the matrix as well as the non-matrix proteins. MMP-2 and MMP-9 belong to the family of gelatinase and are known as gelatinase A and gelatinase B, respectively. [17] Studies have shown that MMP-2 and MMP-9 play a crucial role in the breakdown of blood brain barrier and in the migration of leucocytes in the central nervous system diseases such as multiple sclerosis and tuberculous meningitis. [18],[19] In central nervous system tuberculosis, pro-inflammatory cytokines IL-1β and interferon-γ have been demonstrated to up regulate the MMP-9 level. The latter has been postulated to play a significant role in causing brain tissue damage. [20] Recent studies have revealed the role of MMP-2 and MMP-9 in parasitic infections like Toxoplasma gondii in generating an astroglial reaction and in the recruitment of leucocytes. [21] There is emerging evidence that MMP-2 and MMP-9 may play a significant role in the symptomatology of patients with multiple neurocysticercosis. [22]

In this study, we estimated the serum and CSF cytokines and MMP-2 and 9 levels in patients with a solitary cysticercus granuloma. We also assessed the possible role of baseline cytokines and MMPs on the resolution, persistence or calcification of these lesions.


 » Materials and Methods Top


This case-control study was carried out in a tertiary care hospital from 2009 to 2013. The ethical approval was obtained from the Institutional Ethics Committee. The written informed consent was taken from all the cases and controls (or their guardians), enrolled in the study.

Inclusion criteria

Consecutive patients with new onset seizures (presenting within 7 days of the first seizure) were screened using contrast-enhanced computed tomography of the brain. A solitary cysticercus granuloma was diagnosed on the basis of criteria given by Rajshekhar and co-workers. [7],[23] All our patients had a solitary ring-enhancing lesion measuring less than 20 mm with or without the presence of perilesional edema. [7],[23] [Figure 1].
Figure 1: (a) Contrast enhanced CT scan shows a solitary cysticercus granuloma; (b) CT after 6 months shows complete resolution of the lesion

Click here to view


Exclusion criteria

The patients with systemic diseases, malignancy, tuberculosis, HIV, pregnancy, progressive neurological deficit, raised intracranial tension and hydrocephalus were excluded from the study. Patients with a history of contrast sensitivity or a contraindication to the administration of contrast were also excluded.

Controls

Control CSF and blood samples were obtained from persons undergoing spinal anesthesia for obstructive uropathy and having no clinically active infection.

Patient evaluation

A detailed clinical history was obtained and neurological examination performed in all included subjects. The laboratory tests like complete hemogram, erythrocyte sedimentation rate, fasting blood sugar, renal function tests, liver function tests, C-reactive protein and enzyme-linked immunosorbent assay for human immunodeficiency virus were performed. The site, size and stage of the granuloma were noted along with the presence or absence of perilesional edema. An electroencephalography (EEG), using the 10-20 international system of electrode placement, was also performed.

The sera was separated by centrifugation at 1000 g for 30 minutes; and, aliquots were prepared and immediately stored at −80°C for cytokine analysis. The CSF was collected using a sterile lumbar puncture technique. It was processed immediately for cell count, proteins and sugar levels and the CSF aliquots were prepared and similarly stored at -80°C for the cytokine analysis. The parameters that were analyzed included TNF α, IL-1β, IL-5, IL-6, IL-10, MMP-2 and MMP-9.The tests were done using commercially available human ELISA kits as per the manufacturer's instructions (Bio Legend Max™, San Diego, CA, USA). The ELISA tests were performed in duplicates independently for each sample and the results were expressed as picogram/ml (pg/ml) for all cytokines and MMP-9. The results of MMP-2 were expressed in nanogram/ml (ng/ml).

Treatment

The patients were treated with oxcarbazepine, 10-15mg/kg/day in two divided doses. Those patients who had a recurrence of seizures despite being on treatment were given the additional anticonvulsant, clobazam. In case of seizure recurrence, the patients were advised to report immediately to the investigator-in-charge. None of the patients were treated with albendazole or corticosteroids.

Follow-up

A follow-up computed tomography was done in all the patients at an interval of 6 months. The patients demonstrating partial or incomplete resolution of the lesion were considered to have a persisting lesion. The lesion was considered as "resolved" if the follow up computed tomography was reported as normal. The lesion was considered as "calcified" if the follow up imaging showed a hyperdense lesion in place of the granuloma.

Seizure recurrence was defined as occurrence of another seizure at least 1 week after the institution of the antiepileptic therapy. Status epilepticus was defined either as a continuous seizure activity or as a repetitive seizure activity without resumption of consciousness over a 30 minute period . Three or more seizure episodes were classified as multiple seizure recurrences. Serial seizures were defined as multiple seizures occurring within 24 hours.

Statistical analysis

A sample size of 47 (using a two-sided hypothesis test with a significance level of 0.05, and considering a non-response rate of 20%) was calculated. The entire clinical and the laboratory data was analysed for the normalcy of distribution using the Shapiro-Wilk test. The univariate analysis of non-parametric data was done by using the Mann-Whitney U test. Univariate analysis of the serum and CSF concentrations of TNF α, IL-1β, IL-5, IL-6, IL-10, MMP-2 and MMP-9 between the case and control groups was done using the Mann-Whitney U test. The groups based on the radiological outcome were compared in paired groups such as, persistence of the cyst versus its resolution, resolution of the cyst versus its calcification, and persistence of the cyst versus its calcification. The multivariate analysis was done using the binary logistic regression test. For parametric data, proportions were compared using the Chi-square test. The analysis was carried using SPSS version 16 and a P ≤ 0.05 was considered significant.


 » Results Top


Of the 104 patients with new onset seizures, 57 patients were excluded. 31 patients had more than one granuloma or a conglomerate of lesions. Twenty two patients presented beyond 7 days of onset of the seizures, and 4 patients denied consent for a lumbar puncture. Therefore, 47 patients (30 males and 17 females) were enrolled in the study [Figure 2].
Figure 2: Study algorithm

Click here to view


Baseline clinical features

The baseline demographic, clinical and laboratory characteristics of the included patients have been provided in [Table 1].
Table 1: Baseline clinical and laboratory features of the patients with solitary cysticercus granuloma


Click here to view


Baseline cytokines parameters

The median levels of cytokines IL-1β, IL-5, IL-6, IL-10 and TNF-α, MMP-2 and MMP-9 were significantly elevated in serum and CSF of patients with a solitary cysticercus granuloma compared with that of the controls [Table 2].
Table 2: Serum and CSF cytokines and MMPs levels in patients with a solitary cysticercus granuloma and age sex matched controls compared using Mann Whitney U test


Click here to view


Outcome analysis after 6 months of follow up

The follow up CT revealed that in 27 (57.45%) patients, the lesions were calcified. There was a complete resolution of the lesion in 5 (10.64%) patients. In 15 (31.91%) patients, the lesions remained unchanged.

Seizure recurrence

Fourteen patients had a recurrence of a single or of multiple seizures. The seizure recurrence was found to be more common in patients with EEG abnormalities, and those with high TNF-α and IL-1β levels. The Kaplan Meier analysis revealed a non-significant higher cumulative risk for seizure recurrence in the calcification group [Figure 3]. A high baseline serum TNF-α level was independently associated with seizure recurrence (P = 0.021, OR = 1.041, CI = 1.006 to 1.078).
Figure 3: Kaplan Meier analysis of patterns of seizure recurrence in patients with a solitary cysticercus granuloma

Click here to view


Lesion resolution

A high baseline CSF MMP-2 and a high TNF-α level were associated with persistence of the granuloma. Complete resolution of the lesion was associated with a high baseline serum MMP-2, IL-6 levels and a low baseline CSF IL-10 level. In the "calcified" lesion group, only IL-1β was found to be significantly elevated [Table 3] and [Table 4].
Table 3: Median (range) of CSF levels of MMP and cytokines in various outcome groups among patients with a solitary cysticercus granuloma and age-sex matched controls, and their comparison using Mann Whitney U test


Click here to view
Table 4: Median (range) of serum levels of MMP and cytokines in various outcome groups among patients with a solitary cysticercus granuloma and age-sex matched controls, and their comparison using Mann Whitney U test


Click here to view



 » Discussion Top


We observed that serum and CSF levels of the cytokines (IL-1β, IL-5, IL-6, IL-10 and TNF-α) and MMP-2 and MMP-9 were markedly elevated in our patients with a solitary cysticercus granuloma when compared with controls. Our findings, in fact, indicated that both systemic as well as local inflammatory changes were involved in the pathogenesis of the seizures precipitated by a solitary cysticercus granuloma. Histopathologically, the cysticercus granuloma comprises of a dying cyst surrounded by fibrosis, angiogenesis, and an infiltration of inflammatory cells. The most abundant cell types are the plasma cells, B and T lymphocytes, macrophages, and mast cells. The proinflammatory cytokines (TNF-alpha and IL-1) play a crucial role in the granuloma formation. In a cysticercus granuloma, plenty of both T helper type 1 cytokines and T helper type 2 cytokines have been demonstrated. [24] Viable parasites induce T helper type 2 cells and regulatory cytokines, and suppress the host T helper type 1 response. In contrast, death of the cysticerci is associated predominantly with T helper type 1 cytokines. [11] The brain tissue surrounding the cyst also demonstrates inflammatory changes. Brain specimens were demonstrated to be having a proinflammatory activity as reflected by the altered blood-brain barrier permeability, secretion of pro-inflammatory cytokines, and the up-regulation of molecules responsible for antigenic presentation. There were anti-inflammatory cytokines, and an active wound-healing process, as reflected by angiogenesis, collagen deposition and glial scar formation. [24] Perhaps, some genetic factors trigger the inflammatory reaction in patients with neurocysticercosis. In a study, Toll-like receptor 4 polymorphisms were found to be associated with symptomatic neurocysticercosis. [25]

We observed that MMP-2 and MMP-9 were markedly elevated in patients with a solitary cysticercus granuloma. MMPs also play a significant role in the generation or perpetuation of these inflammatory changes. MMPs accomplish tissue remodelling via degradation of the extracellular matrix. Integrity or disruption of the blood brain barrier plays a crucial role in the pathogenesis of inflammatory changes seen in the cysticercus granuloma. MMP-2 and MMP-9 are two of the most widely studied enzymes that have been shown to be critical in regulating blood-brain barrier permeability. Several studies in animals have suggested that breakdown of the blood-brain barrier occurs because of the high activity of MMP-9. [26] In humans, too, MMP-2 and MMP-9 have been shown to play an important role in the development of symptoms. [22]

We observed that higher levels CSF IL-1β and serum TNF-α were associated with seizure recurrence in patients with a solitary cysticercus granuloma who present with an acute seizure disorder. Recurrent seizures and Todd's paralysis (that quickly resolves), are frequently observed. The seizures in neurocysticercosis are thought to result from the inflammatory response to the release of parasitic antigens at the time of transformation of the vesicular stage to the inflammatory colloidal stage. Is it possible that an inflammatory substance produced by the cysticercus granuloma initiates the epileptiform activity? In a study, several pieces of granulomas (Taenia crassiceps) were removed from the peritoneal cavity of mice. A piece of the granuloma was used for histological staging of the dying parasite and the second piece was used to generate extracts, which were injected into the hippocampus of rat. Seizures were noted after injection of the extracts prepared from the early-stage granulomas, but not with those from the late-stage granulomas. This observation suggested that there was an epileptogenic element in the early-stage granulomas. [27] It was later shown that the levels of cytokines were not significantly different between the early- and the late- stage granulomas. Thus, it was thought that proinflammatory cytokines were possibly not responsible for seizures. [28] Substance P evokes epileptiform activity, whereas, somatostatin has anticonvulsant properties. Both possibly play a role in the pathogenesis of seizures in neurocysticercosis. The neuropeptide substance P also stimulates growth of the granuloma and the production of T helper 1 type cytokines. Somatostatin stimulates T helper type 2 cytokine production and impairs the granuloma formation. Pretreatment with substance P receptor antagonist inhibited the seizures induced by extracts from the early granulomas. Similarly, injection of substance P into the rat brain induced seizures and altered the hippocampal activity that was blocked by substance P receptor antagonist or somatostatin. [29],[30] We suggest that, in humans too, marked elevation of TNF-α and other cytokines may be responsible for the development of seizures.

The reason why some cysticercus granulomas resolve completely while others get calcified is not precisely known. We also explored if the inflammatory profile observed, helped in predicting the disappearance or calcification of the lesion. This fact is important because if a lesion persists or gets calcified, it may act as a source of epileptogenic activity. We found that a lower serum MMP-2, a lower serum IL-6 and a higher CSF TNF-α level were associated with an unresolved cysticercus granuloma. We observed a significant association of resolution of the lesion with serum IL-6 and CSF IL-10, while CSF IL-1β correlated with calcification of the lesion. Our findings indicate that a balance in the pro-inflammatory and regulatory inflammatory response is crucial for the complete resolution of the granuloma. Increased blood-brain barrier permeability in a calcified lesion is probably secondary to the perilesional inflammation. This impaired blood-brain barrier, secondary to inflammation, may result in penetration of plasma proteins into the brain parenchyma and may result in seizure recurrence in conjunction with a calcified lesion. [31]

Our study had certain limitations. The group showing resolution of the parasite was small. A follow-up cytokine and MMP profile in the serum and CSF might have helped us in understanding the variability in the radiological outcome. This would have also eliminated the influence of seizures on the cytokine and MMP levels as all the enrolled patients were seizure-free by the end of 6 months of follow-up. Another limitation in our study was that, due to ethical reasons, we did not include as controls, patients who were suffering from epilepsy but did not have the presence of a solitary cysticercus granuloma. Seizures by themselves can cause an increase of inflammatory factors.

In patients with a solitary cysticercus granuloma, cytokines and matrix metalloproteinases in CSF and serum are elevated. Different patterns of immunological changes were observed in patients following resolution or calcification of the lesion.

 
 » References Top

1.
Prasad KN, Prasad A, Verma A, Singh AK. Human cysticercosis and Indian scenario: A review. J Biosci 2008;33:571-82.  Back to cited text no. 1
    
2.
Prasad KN, Prasad A, Gupta RK, Pandey CM, Uttam S. Prevalence and associated risk factors of T. solium taeniasis in a rural pig farming community of North India. Trans R Soc Trop Med Hyg 2007;101:1241-7.  Back to cited text no. 2
    
3.
Rajshekhar V, Raghavan MV, Prabhakaran V, Oommen A, Muliyil J. Active epilepsy as an index of burden of neurocysticercosis in Vellore district, India. Neurology 2006;67: 2135-9.  Back to cited text no. 3
    
4.
Singhi PD, Baranwal AK. Single small enhancing computed tomographic lesions in Indian children-II. Clinical features, pathology, radiology and management. J Trop Pediatr 2001;47:266-70.  Back to cited text no. 4
    
5.
Garg RK, Malhotra HS. Solitary cysticercus granuloma. Expert Rev Anti Infect Ther 2012;10:597-612.  Back to cited text no. 5
    
6.
Rajshekhar V, Haran RP, Prakash GS, Chandy MJ. Differentiating solitary small cysticercus granulomas and tuberculomas in patients with epilepsy. Clinical and computerized tomographic criteria. J Neurosurg 1993;78:402-7.  Back to cited text no. 6
    
7.
García HH, Gonzalez AE, Rodriguez S, Tsang VC, Pretell EJ, Gonzales I, et al. Neurocysticercosis: Unravelling the nature of the single cysticercal granuloma. Neurology 2010;75:654-8.  Back to cited text no. 7
    
8.
Sharma K, Wahi J, Phadke RV, Varma A, Jain VK. Migraine-like visual hallucinations in occipital lesions of cysticercosis. J Neuroophthalmol 2002;22:82-7.  Back to cited text no. 8
    
9.
Karnik PS, Tullu MS, David JJ, Ghildiyal RG. Neurocysticercosis-induced hemiballismus in a child. J Child Neurol 2011;26:904-6.  Back to cited text no. 9
    
10.
Khurana N, Sharma P, Shukla R, Singh D, Vidhate M, Naphade PU. Midbrain neurocysticercosis presenting as isolated pupil sparing third cranial nerve palsy. J Neurol Sci 2012;312:36-8.  Back to cited text no. 10
    
11.
Sujit Kumar GS, Rajshekhar V. New solitary cysticercus granulomas causing recurrent symptoms in patients with resolved solitary granulomas. Neurol India 2004;52:265-7.  Back to cited text no. 11
    
12.
Agarwal A, Raghav S, Husain M, Kumar R, Gupta RK. Epilepsy with focal cerebral calcification: Role of magnetization transfer MR imaging. Neurol India 2004;52:197-9.  Back to cited text no. 12
[PUBMED]  Medknow Journal  
13.
Singh G, Murthy JM. Solitary cysticercus granuloma-treatment with albendazole: What is the optimal duration? Neurol India 2010;58:507-8.  Back to cited text no. 13
[PUBMED]  Medknow Journal  
14.
Restrepo BI, Alvarez JI, Castaño JA, Arias LF, Restrepo M, Trujillo J, et al. Brain granulomas in neurocysticercosis patients are associated with a Th1 and Th2 profile. Infect Immun 2001;69:4554-60.  Back to cited text no. 14
    
15.
Rooker S, Jander S, Van Reempts J, Stoll G, Jorens PG, Borgers M, et al. Spatiotemporal pattern of neuroinflammation after impact-acceleration closed head injury in the rat. Mediators Inflamm 2006;2006:90123.  Back to cited text no. 15
    
16.
Choi J, Min HJ, Shin JS. Increased levels of HMGB1 and pro-inflammatory cytokines in children with febrile seizures. J Neuroinflammation 2011;8:135.  Back to cited text no. 16
    
17.
Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry. Circ Res 2003;92:827-39.  Back to cited text no. 17
    
18.
Abraham M, Shapiro S, Karni A, Weiner HL, Miller A. Gelatinases (MMP-2 and MMP-9) are preferentially expressed by Th1 vs. Th2 cells. J Neuroimmunol 2005;163:157-64.  Back to cited text no. 18
    
19.
Lee KY, Kim EH, Yang WS, Ryu H, Cho SN, Lee BI, et al. Persistent increase of matrix metalloproteinases in cerebrospinal fluid of tuberculous meningitis. J Neurol Sci 2004;220:73-8.  Back to cited text no. 19
    
20.
Harris JE, Fernandez-Vilaseca M, Elkington PT, Horncastle DE, Graeber MB, Friedland JS. IFN gamma synergizes with IL-1beta to up-regulate MMP-9 secretion in a cellular model of central nervous system tuberculosis. FASEB J 2007;21:356-65.  Back to cited text no. 20
    
21.
Lu CY, Lai SC. Matrix metalloproteinase-2 and -9 lead to fibronectin degradation in astroglia infected with Toxoplasma gondii. Acta Trop 2013;125:320-9.  Back to cited text no. 21
    
22.
Verma A, Prasad KN, Nyati KK, Singh SK, Singh AK, Paliwal VK, et al. Association of MMP-2 and MMP-9 with clinical outcome of neurocysticercosis. Parasitology 2011;138:1423-8.  Back to cited text no. 22
    
23.
Rajshekhar V, Chandy MJ. Validation of diagnostic criteria for solitary cerebral cysticercus granuloma in patients presenting with seizures. Acta Neurol Scand 1997;96:76-81.  Back to cited text no. 23
    
24.
Alvarez JI, Colegial CH, Castaño CA, Trujillo J, Teale JM, Restrepo BI. The human nervous tissue in proximity to granulomatous lesions induced by Taenia solium metacestodes displays an active response. J Neuroimmunol 2002;127:139-44.  Back to cited text no. 24
    
25.
Verma A, Prasad KN, Gupta RK, Singh AK, Nyati KK, Rizwan A, et al. Toll-like receptor 4 polymorphism and its association with symptomatic neurocysticercosis. J Infect Dis 2010;202:1219-25.  Back to cited text no. 25
    
26.
Taylor JL, Hattle JM, Dreitz SA, Troudt JM, Izzo LS, Basaraba RJ, et al. Role for matrix metalloproteinase 9 in granuloma formation during pulmonary Mycobacterium tuberculosis infection. Infect Immune 2006;74:6135-44.  Back to cited text no. 26
    
27.
Stringer JL, Marks LM, White AC Jr, Robinson P. Epileptogenic activity of granulomas associated with murine cysticercosis. Exp Neurol 2003;183:532-6.  Back to cited text no. 27
    
28.
Patil S, Robinson P, Actor JK, Baig S, White AC Jr. Proinflammatory cytokines in granulomas associated with murine cysticercosis are not the cause of seizures. J Parasitol 2006;92:738-41.  Back to cited text no. 28
    
29.
Garza A, Tweardy DJ, Weinstock J, Viswanathan B, Robinson P. Substance P signaling contributes to granuloma formation in Taenia crassiceps infection, a murine model of cysticercosis. J Biomed Biotechnol 2010;2010:597086.  Back to cited text no. 29
    
30.
Robinson P, White AC, Lewis DE, Thornby J, David E, Weinstock J. Sequential expression of the neuropeptides substance P and somatostatin in granulomas associated with murine cysticercosis. Infect Immun 2002;70:4534-8.  Back to cited text no. 30
    
31.
Ooi WW, Wijemanne S, Thomas CB, Quezado M, Brown CR, Nash TE. A calcified Taenia solium granuloma associated with recurrent perilesional edema causing refractory seizures: Histopathological features. Am J Trop Med Hyg 2011;85:460-3.  Back to cited text no. 31
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

This article has been cited by
1 TNF-a blockade suppresses pericystic inflammation following anthelmintic treatment in porcine neurocysticercosis
Siddhartha Mahanty,Miguel A. Orrego,Carla Cangalaya,M. Paz Adrianzen,Gianfranco Arroyo,Juan Calcina,Armando E. Gonzalez,Héctor H. García,Cristina Guerra-Giraldez,Theodore E. Nash,Ricardo Toshio Fujiwara
PLOS Neglected Tropical Diseases. 2017; 11(11): e0006059
[Pubmed] | [DOI]
2 New diagnostic criteria for neurocysticercosis: Reliability and validity
Arturo Carpio,Agnès Fleury,Matthew L. Romo,Ronaldo Abraham,Jaime Fandiño,Juan C. Durán,Graciela Cárdenas,Jorge Moncayo,Cleonísio Leite Rodrigues,Daniel San-Juan,Marcos Serrano-Dueñas,Oswaldo Takayanagui,Josemir W. Sander
Annals of Neurology. 2016; 80(3): 434
[Pubmed] | [DOI]



 

Top
Print this article  Email this article
   
Online since 20th March '04
Published by Wolters Kluwer - Medknow