flunarizine and Hematoma

This study aimed to explore the role and mechanism(s) of flunarizine hydrochloride in the intracerebral hemorrhage (ICH) rats. The 32 adult male Sprague Dawley (SD) rats were randomly assigned into four groups: control group, sham group, ICH group, and FLU + ICH group. The effects of flunarizine hydrochloride were assessed on the basis of hematoma volume, blood-brain barrier (BBB) integrity, and brain water content in the ICH rat models. The role of flunarizine hydrochloride in cell recovery was assessed by behavioral scores, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot assay. Involvement of PI3K/AKT pathway in exerting the effect of flunarizine hydrochloride was also determined. Results showed that the hematoma volume, BBB integrity, and brain water content were significantly decreased in the FLU + ICH group. Cell apoptosis significantly increased in the ICH model group, while flunarizine hydrochloride decreased this increase. The expressions of glial cell line-derived neurotrophic factor (GDNF), neuroglobin (NGB), and p-AKT were increased after flunarizine hydrochloride treatment in ICH rats. In conclusion, flunarizine hydrochloride has protective effects against ICH by reducing brain injury, cell apoptosis, and the activation of P13K/AKT pathway. These findings provide a theoretical basis for the treatment of flunarizine hydrochloride in ICH.

Topics: Animals; Apoptosis; Behavior, Animal; Blood-Brain Barrier; Brain; Brain Injuries; Calcium Channel Blockers; Cerebral Hemorrhage; Edema; Flunarizine; Glial Cell Line-Derived Neurotrophic Factor; Globins; Hematoma; Male; Nerve Tissue Proteins; Neuroglobin; Neurons; Neuroprotective Agents; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Rats, Sprague-Dawley; Water

In 25 rats, an intracerebral hematoma was created in the foreleg area of the motor cortex by injection of 50 microliters blood. After the lesion, 13 were treated with flunarizine and 12 with the solvent. Neurological testing was performed by measuring the running time on a rotating platform. In animals with hemiparesis, the flunarizine group (n = 7) showed a significantly (P less than 0.05) better recovery than the control group (n = 8). No significant differences occurred in animals without neurological deficits (flunarizine: n = 6, control: n = 4). So the effect of the drug is not due to a non-specific activation; it may partially cure neurological deficits caused by intracerebral hematoma.

Topics: Animals; Cerebral Cortex; Cerebral Hemorrhage; Flunarizine; Hematoma; Hemiplegia; Locomotion; Male; Rats; Rats, Inbred Strains; Time Factors