Seizures induced by intracerebral injection of thrombin: a model of intracerebral hemorrhage

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Abstract
The coagulation cascade plays an important role in brain edema formation caused by intracerebral blood. In particular, thrombin produces brain injury via direct brain cell toxicity. Seizures and increased cerebral electrical activity are commonly associated with intracerebral blood and are possible effects of thrombin leading to cell injury in the brain. In this study, artificial clots containing concentrations of thrombin found in hematomas were infused intracerebrally in rats. The animals were observed clinically for seizure activity, behavior, and neurological deficits. Several animals underwent video electroencephalographic (EEG) monitoring during intracerebral infusion and for 30 minutes postinfusion. All animals were killed 24 hours after injection, and brain water and ion contents were measured to determine the amount of brain edema. Clinically, thrombin produced focal motor seizures in all animals. None of the control animals or those receiving N[alpha]-(2-Naphthalenesulfonyl-glycyl)-4-amidino-DL-phenylalanine -piperidide (alpha-NAPAP), a thrombin inhibitor added to the thrombin, showed clinical evidence of seizures. Of the rats undergoing EEG monitoring, all animals receiving thrombin showed electrical evidence of seizure activity, whereas none of the control animals exhibited seizure activity. There was no evidence of seizure activity on EEG monitoring when alpha-NAPAP was injected along with the thrombin. In addition, the artificial clots containing thrombin produced agitation and a circling tendency in the rats, along with brain edema. These results indicate that the coagulation cascade is involved in seizure production and increased brain electrical activity, which contribute to the neurological deficits and brain edema formation that are seen with intracerebral hemorrhage.