Background and Purpose: We previously reported the neuroprotective effects of trans-arterial regional hypothermia in rat transient middle cerebral artery occlusion (tMCAO) model (ISC 2014, ISC 2015). The tMCAO model is representative of the clinical setting of successful recanalization in acute ischemic stroke. However, it is not always possible to achieve successful recanalization. Herein, we investigated the neuroprotective effects of trans-arterial regional hypothermia in permanent MCAO (pMCAO) model as well.
Methods: Three groups were provided to investigate the neuroprotective effects. Regional hypothermia group had a single infusion of 20ml/kg 10°C cold saline via the ipsilateral internal carotid artery for 15 min at 0 hr or 1 hr after the onset of pMCAO. Vehicle group had a 37°C warm saline infusion in the same manner. Control group had no infusion after pMCAO. The rats were tested for neurological score after 48-hour pMCAO and then sacrificed to evaluate infarction size and pathological condition. Immunohistochemical analysis was performed to investigate the neuronal apoptosis (NeuN, cleaved caspase 3), glial reaction (GFAP), and microglial activation (Iba-1).
Results: The regional hypothermia group showed significantly better neurological score compared with the other groups (p<0.01). Infarct volume was significantly smaller in the regional hypothermia group (8.1±4.7% at 0 hr and 15.7±5.9% at 1 hr) than in the vehicle group (35.8±5.6% at 0 hr and 34.0±3.6% at 1 hr) and also in the control group (35.1±8.9%) (p<0.01). Neuronal apoptosis (p<0.01), reactive gliosis (p<0.01), and microglial activation (p<0.05) in the peri-infarct area were significantly inhibited in the regional hypothermia group compared with the other groups. The degree of the inhibition was somewhat more evident at 0 hr than at 1 hr.
Conclusions: Our result demonstrated that trans-arterial regional hypothermia provided robust neuroprotection in pMCAO model as well as tMCAO model, suggesting that this therapy may have a wide clinical application in ischemic stroke treatment.