Experimentally induced various inflammatory models and seizure: understanding the role of cytokine in rat.
BACKGROUND
The mechanism of epileptogenesis is not well established. There is higher incidence of seizures among patients with chronic inflammatory disease. Cytokines are rapidly induced in the brain after a variety of stimuli including inflammation. Aim of this study was to produce various inflammatory models and seizure to understand the role of TNFalpha in above mentioned models.


METHODS
A total of 54 male rats were included in the study. Animals were divided into 3 groups of colitis, arthritis, and cotton wool granuloma. Each group had 3 subgroups of control, model and treatment. At the end of 3 days in colitis, 17 days in arthritis and 7 days in cotton wool granuloma groups a subconvulsive dose of PTZ (40 mg/kg i.p) was injected to note seizure onset and seizure score. Brain samples were subjected to DNA fragmentation testing. Presence of inflammation was confirmed by morphology and histology. Plasma and brain TNFalpha levels were measured.


RESULTS
The models of colitis, arthritis and CWG were effectively produced as evidenced by morphology and histology scores (p<0.001). Seizure onset was reduced and grade was increased (p<0.001). Thalidomide reduced the morphological, histological (p<0.002), DNA fragmentation and seizure grade (p<0.001) while increased seizure onset (p<0.001) in the arthritis group. TNFalpha levels in both plasma and brain were reduced following thalidomide treatment (p<0.002) in arthritis group. There were no significant findings in colitis or cotton wool granuloma groups.


CONCLUSIONS
Inflammation was associated with decreased threshold to PTZ induced seizure. Thalidomide is effective in reducing the extent of arthritis as well as reducing the seizure scoring and increasing seizure onset in the adjuvant arthritis group. Thalidomide was also effective in reducing TNFalpha levels thus contributing to its antiepileptic activity.
Rao
R S
RS
Department of Pharmacology, Postgraduate Institute of Medical Education & Research, Chandigarh PGIMER, Chandigarh, India.
Medhi
B
B
Saikia
U N
UN
Arora
S K
SK
Toor
Jaideep S
JS
Khanduja
K L
KL
Pandhi
P
P
D019342:Acetic Acid / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D000077613:Etoricoxib; D005620:Freund's Adjuvant / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013450:Sulfones / Q000627:therapeutic use; D013792:Thalidomide / Q000627:therapeutic use
D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007166:Immunosuppressive Agents; D011725:Pyridines; D013450:Sulfones; D013792:Thalidomide; D005620:Freund's Adjuvant; D019342:Acetic Acid; D000077613:Etoricoxib