Effects of timing of dexamethasone treatment on the outcome of collagenase-induced intracerebral hematoma in rats.
The effect of timing in providing dexamethasone treatment after intracerebral hematoma was evaluated in rats with hematoma induced by a subcortical collagenase injection. Male Sprague-Dawley rats (n = 30; body weight, 185 to 230 g) received dexamethasone (1 mg/kg) intraperitoneally at 2 h, 4 h, or 6 h (1 group per time point) after intracerebral collagenase injection, with another dose (1 mg/kg) administered at 24 h after collagenase injection. Neurologic examinations and rotarod treadmill tests were used to evaluate motor behavior before and at 24 and 48 h after intracerebral injection. Rats were euthanized after the last behavioral test. Brains were evaluated for hematoma size, number of penumbral necrotic neurons, neutrophils within the hematoma, and astrocytic response. Compared with the control and other treatment groups, rats treated with dexamethasone at 2 and 24 h after intracerebral collagenase injection scored significantly better on neurologic exams and rotarod tests. Hematoma volume was significantly smaller in all treated groups than in the control group but did not differ between treatment groups. Fewer neutrophils were seen in the perihematoma region of all treated rats compared with controls, but the number of necrotic neurons was decreased significantly only in the group treated with dexamethasone at 2 and 24 h. These results indicate that a 1-mg/kg dose of dexamethasone is beneficial for treatment of intracerebral hemorrhage, particularly if administered early after the hemorrhagic insult.
Savard
Claudine
C
Department of Microbiology and Pathology, St-Hyacinthe, Québec, Canada.
Lema
Pablo Patricio
PP
Hélie
Pierre
P
Vachon
Pascal
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D017364:Collagenases / Q000008:administration & dosage / Q000633:toxicity; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006407:Hematoma, Epidural, Cranial / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test / Q000379:methods; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D017364:Collagenases