ABSTRACT
Free radical mechanisms are involved in secondary brain injury after intracerebral hemorrhage (ICH). Since melatonin is a potent free radical scavenger and indirect antioxidant, the objective of this study was to evaluate whether melatonin administration would attenuate oxidative stress, brain edema, and neurological deficits in a rat model of ICH. Animals were assigned into groups consisting of sham (needle trauma), vehicle, and melatonin (15 or 150 mg/kg). All injections occurred through the intraperitoneal route, at either 15 min or 3 h after collagenase ICH induction. Then, lipid peroxidation, neurological scoring (18-point system), and brain water content were evaluated at 24h post-ICH. Results demonstrated dramatically increased lipid peroxidation after collagenase-induced ICH; however, melatonin treatment effectively attenuated this lipid peroxidation. Nonetheless, neurological scoring and brain water content in the right basal ganglia was without significant difference between any treatment regimens (15 or 150 mg/kg of melatonin) or time points of drug administration (15 min or 3 h post-ICH). Therefore, melatonin reduced oxidative stress but did not change extent of brain edema or neurologic deficits.
Subject(s)
Antioxidants/therapeutic use , Cerebral Hemorrhage/drug therapy , Melatonin/therapeutic use , Animals , Basal Ganglia/drug effects , Basal Ganglia/pathology , Brain Edema/etiology , Brain Edema/pathology , Brain Edema/prevention & control , Cerebral Hemorrhage/chemically induced , Collagenases , Disease Models, Animal , Dose-Response Relationship, Drug , Lipid Peroxidation/drug effects , Male , Neurologic Examination , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
Free radical scavengers have been shown to improve short-term outcome after intracerebral hemorrhage (ICH). The purpose of this study was to evaluate whether melatonin (a potent free radical scavenger and an indirect antioxidant) can improve short- and/or long-term neurological function after ICH, which was induced by collagenase injection into the striatum of adult rats. Melatonin (15 mg/kg) was administered by intraperitoneal injection at 1, 24, 48, and 72 h. Neurological and behavioral testing was performed at several time points from 1 day to 8 weeks post-ICH. Neurological and behavioral deficits were observed in ICH rats at all time points, but the melatonin treatment regimen did not improve performance or level of brain injury.
Subject(s)
Antioxidants/therapeutic use , Cerebral Hemorrhage/drug therapy , Melatonin/therapeutic use , Animals , Behavior, Animal/drug effects , Brain Infarction/drug therapy , Brain Infarction/etiology , Cerebral Hemorrhage/chemically induced , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/pathology , Collagenases , Corpus Striatum/drug effects , Disease Models, Animal , Exploratory Behavior/drug effects , Male , Motor Activity/drug effects , Neurologic Examination , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
Approximately 15% of all strokes are due to intracerebral hemorrhage (ICH) and of these, 5-10% occur in the cerebellum. The resultant mortality is around 20-30%. However, there is no well-established animal model to address this important clinical problem. We induced intracerebellar hemorrhage in rats using stereotaxic collagenase injection through a burr-hole into right cerebellum. Dosage-dependent effect of collagenase (0.2, 0.4, and 0.6 U) was tested in male and female rats. Brain edema formation was assessed by brain water content and hemorrhagic volume measured by hemoglobin assay. Wire suspension, inclined plane, beam walking, and neurological deficit score assessed neurological outcome. Marked hematoma was observed in right cerebellum, accompanied by brain edema in a dose-related fashion. When comparing sexes, hemorrhagic volume and neurological deficit scores were significantly increased in females compared to male counterpart. Females had mortality of 16%, while there was no mortality in male rats. Neurological deficits assessed by both beam walking and inclined plane were significantly increased at 0.4 and 0.6 U in females, but only at 0.6 for males. This new cerebellar hemorrhage rat model demonstrated dosage- and sex-dependent changes in hemorrhagic volume, brain edema, and neurological deficits, and could be used to test treatment strategies for ICH.
Subject(s)
Cerebellum/physiopathology , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/pathology , Disease Models, Animal , Analysis of Variance , Animals , Brain Edema/etiology , Female , Forelimb/physiopathology , Locomotion/physiology , Male , Muscle Strength/physiology , Nervous System Diseases/etiology , Proprioception/physiology , Psychomotor Performance/physiology , Rats , Rats, Sprague-DawleyABSTRACT
Approximately 15% of all strokes are due to intracerebral hemorrhage, and of these, 5 to 9% will occur in the pons, with mortality approximately 60% of the time. However, there is not an adequate animal model to fully address this important clinical problem. To this end, pontine hemorrhage was induced in rats using stereotaxic injection of 0.15 units of collagenase. At 24, 48, and 72h (n = 4 per group), the hemorrhagic volume, brain water content, body temperature, and neurological function (corner turn, inclined plane, and neurological deficit score) were assessed. All tested parameters were significantly increased, compared to sham, without any differences between time points. Furthermore, the extent of brainstem edema was highly correlated with neurological score, inclined plane, and body temperature. This new pontine hemorrhage rat model demonstrated brain edema and neurological deficits, and can be used to test treatment strategies for pontine hemorrhage.
