Attenuation of secondary lesion growth in the brain after trauma by selective inhibition of the inducible NO-synthase.
In previous studies we have demonstrate that aminoguanidine pretreatment attenuates the secondary necrosis growth after focal brain trauma. Purpose of the present investigation was to elucidate the therapeutic potential of this iNOS-inhibitor when administered post lesion. Sprague-Dawley rats were subjected to a highly standardized cortical freezing lesion and administered with aminoguanidine (100 mg/kg i.p.) 15 min and 8 hrs after trauma or with isotonic saline, respectively. Animals were assigned to one of three experimental groups. The animals of group I--which served as reference for the histomorphometric determination of the spread of the primary lesion--were sacrificed 5 min after trauma. Group II, receiving isotonic saline and group III with aminoguanidine were subjected to perfusion fixation 24 hrs after trauma for evaluation of the necrosis growth. In controls with saline, the volume of the cortical necrosis increased from 6.07 +/- 1.04 mm3 (5 min) to 8.39 +/- 1.57 mm3 at 24 hrs (group II) after trauma. Treatment with aminoguanidine (group III) led to significant attenuation of the expansion of the necrosis to 6.77 +/- 0.87 mm3 at 24 hrs. Thus, the pathological role of activation of the inducible NO-synthase in the phenomenon of secondary lesion growth is confirmed by the present data on iNOS-inhibition. Attenuation of expansion of the lesion is achieved even when initiating therapy after trauma.
Stoffel
M
M
Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Rinecker
M
M
Plesnila
N
N
Eriskat
J
J
Baethmann
A
A
D000818:Animals; D001925:Brain Damage, Chronic / Q000473:pathology*; D001929:Brain Edema / Q000473:pathology*; D001930:Brain Injuries / Q000473:pathology*; D002540:Cerebral Cortex / Q000293:injuries* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D006146:Guanidines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine