Prolonged Localized Mild Hypothermia Does Not Affect Seizure Activity After Intracerebral Hemorrhage in Rats

Intracerebral hemorrhage (ICH) is a devastating stroke with high morbidity and mortality. Post-ICH seizures are a common complication, potentially increasing brain injury and the risk of delayed epilepsy. Mild therapeutic hypothermia (HYPO, similar to 33 degrees C) is neuroprotective against several brain insults, such as ischemia, while also mitigating seizure incidence and severity in some instances. Therefore, we tested whether brain-selective HYPO reduced electrographic seizure activity after a collagenase-induced striatal ICH in rats. Animals were injected unilaterally with 0.14 U of bacterial collagenase, implanted with a unilateral brain cooling device, and a probe to bilaterally record electroencephalographic (EEG) activity. Cooling began 6 hours after collagenase infusion and was maintained for 48 hours, followed by rewarming over 6 hours. Our protocol did not affect EEG activity in naive rats, nor did it increase bleeding after ICH (similar to 50 mu L). Epileptiform activity commonly occurred in untreated ICH rats (similar to 60% of animals), but HYPO did not affect the incidence, timing, total duration of seizures, or the peaks occurring during epileptiform activity. However, longer average duration was detected on the ipsilateral side to stroke in the HYPO group (p < 0.05). Cooling did not affect neurological deficits (e.g., circling), measured 7 and 14 days after ICH, or lesion volume (similar to 35 mm(3)). In addition, there was no relationship among endpoints (e.g., seizures and lesion size). In summary, HYPO failed to reduce seizure activity after ICH, which fits with our separate findings that cooling does not mitigate thrombin and iron-mediated secondary injury mechanisms thought to cause seizures after ICH. Additional research is needed to identify better HYPO protocols and the use of cotreatments to maximize the benefit of HYPO to ICH patients.