Secondary growth of a cortical necrosis: effect of NOS inhibition by aminoguanidine post insult.
BACKGROUND
A cortical tissue necrosis from a focal freezing injury expands to 140% of its initial volume within 24 hrs in rats. Previous studies of our laboratory have shown that administration of the NOS inhibitor aminoguanidine (AG) prior to trauma attenuates this process of secondary brain damage. Objective of the present study was to analyse whether this agent is also protective when treatment commences after the insult.


METHODS
A highly standardized freezing lesion was induced in the brain cortex of 30 anaesthetized rats. The animals were divided into three experimental groups. Animals of group I (sham-5 min, n=10) were sacrificed 5 min after trauma for quantitative histomorphometric assessment of the primary cortical lesion. Animals of group II (sham-24 h, n=10) received isotonic saline (16.7 ml/kg b.w., i.p.) at 15 min and 8 hrs after trauma. In the treatment group (group III, AG-24 h, n=10), AG was administered (100 mg/kg b.w.) also at 15 min and 8 hrs after trauma. 24 hrs later--the time point of maximal lesion spread--the animals of group II and III were sacrificed for quantification of the secondary lesion growth.


RESULTS
The focal freezing injury produced a cortical necrosis volume of 6.07+/-1.04 mm(3) immediately after trauma (group I). After sham treatment, the necrosis expanded to 8.39+/-1.57 mm(3) within 24 hrs (group II) corresponding to a lesion growth of 138% compared to the primary necrosis ( p<0.01 vs. group I). In animals treated with AG after the trauma (group III), the volume of necrosis was significantly attenuated at 24 hrs to 6.77+/-0.87 mm(3) representing an expansion of the lesion to only 112% ( p<0.05 vs. group II). Thus, AG was inhibiting the secondary growth of necrosis by no less than 69%.


CONCLUSIONS
The findings demonstrate that AG retains its neuroprotective potential against secondary brain damage from trauma even when administration begins after trauma.
Rinecker
M
M
Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Plesnila
N
N
Baethmann
A
A
Stoffel
M
M
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000293:injuries* / Q000473:pathology*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006146:Guanidines / Q000008:administration & dosage*; D008297:Male; D009336:Necrosis; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006146:Guanidines; D018696:Neuroprotective Agents; D019001:Nitric Oxide Synthase; C004479:pimagedine