Effects of nitric oxide on dentate gyrus cell proliferation after seizures induced by pentylenetrazol in the adult rat brain.
Epileptic seizures have been shown to increase the proliferation of granule cell precursors in the adult brain, but the underlying mechanisms remain largely unknown. This study examined the effect of nitric oxide (NO) on the proliferation of granule cell precursors in adult rats after pentylenetrazol (PTZ)-induced generalized clonic seizures. Using systemic bromodeoxyuridine (BrdU) to label dividing cells, we found that injection of the neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (50 mg/kg i.p.) 10 min before PTZ significantly reduced the number of BrdU labeled cells in the dentate gyrus 3, 7, and 14 days after seizures (P < 0.05). Administration of the inducible NOS (iNOS) inhibitor aminoguanidine (100 mg/kg i.p.) also significantly inhibited the proliferation rate of neural precursor cells in the dentate gyrus at various time points after PTZ-induced seizures. Our findings suggest that epileptic seizures lead to increased cell proliferation in the adult rat dentate gyrus through NO-dependent mechanisms. Both the NO originating from nNOS and iNOS may be involved in brain repair after seizures.
Jiang
Wen
W
Neuropsychiatry Research Unit, A114 Medical Research Building, University of Saskatchewan, 103 Wiggins Road, Saskatoon, Canada S7N5E4. wen.jiang@usask.ca
Xiao
Lan
L
Wang
Jin-Cun
JC
Huang
Yuan-Gui
YG
Zhang
Xia
X
D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count / Q000379:methods; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000473:pathology*; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology* / Q000627:therapeutic use; D010433:Pentylenetetrazole; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D013997:Time Factors
D016166:Free Radical Scavengers; D009569:Nitric Oxide; D001973:Bromodeoxyuridine; D010433:Pentylenetetrazole