Nimodipine treatment to assess a modified mouse model of intracerebral hemorrhage.
One of the main limitations of intracerebral hemorrhage (ICH) research is lack of reproducible animal models. ICH appears to be associated with a volume of edema and ischemic injury surrounding the hematoma that may be reduced by nimodipine due to its vasodilating and cytoprotective effects. The present study was designed to produce a modified ICH model in mice based on the double-injection method initially developed by Dr. Belayev and accordingly performed in 3 groups: to evaluate this model itself and to assess the pharmacological effects of nimodipine in this model, respectively. In 80 ICR mice (32 +/- 3 g), ICH was induced by 30 microL whole blood injection into the caudate nucleus. ICH animals were then randomly received either nimodipine (5 mg/kg) or vehicle intraperitoneal injection just before and every 24 h after ICH (total of four times). The changes for cortical blood flow (CBF) were studied by the technique of Laser Doppler Perfusion Measure (LDPM). Animals were rated on a behavioral test and sacrificed at 72 h after ICH. The brains were removed, and hematoma volume and brain edema were subsequently determined. Due to the vasodilating effect of nimodipine, ICH animals treated with nimodipine had marked improved CBF accompanied by the improvement of forelimb placing performance compared with vehicle-treated ICH animals, though there was no marked difference in the hematoma volume and brain water content. In conclusion, the 30 microL whole blood injection closely mimicked natural ischemic events that occurred in human massive ICH and confirmed the anti-ischemia effect of nimodipine. This study suggested that nimodipine could be markedly effective to reduce edema and hematoma volume when administered in combination with other neuroprotective agents because ICH can induce brain injury by multiple mechanisms.
Ma
Bo
B
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Zhang
Jianjun
J
D000704:Analysis of Variance; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000188:drug therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D007839:Functional Laterality; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009553:Nimodipine / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D013997:Time Factors; D014867:Water / Q000378:metabolism
D002121:Calcium Channel Blockers; D014867:Water; D009553:Nimodipine