Transarterial regional hypothermia provides robust neuroprotection in a rat model of permanent middle cerebral artery occlusion with transient collateral hypoperfusion

- Transarterial regional hypothermia has neuroprotective effects on transient ischemia.
- We used a model of permanent middle cerebral artery occlusion (MCAO) with transient collateral hypoperfusion.
- Cold infusion was neuroprotective for the penumbra in spite of persistence of MCAO.
- The results suggest the wider application of this therapy in clinical settings.

The robust neuroprotective effects of transarterial regional hypothermia have been demonstrated in the typical transient middle cerebral artery occlusion (tMCAO) model, but have not yet been tested in other ischemic stroke models, even though clinical ischemic conditions are diverse. In order to clarify these effects in a different ischemic stroke model, we employed a rat model of permanent MCAO (pMCAO) with transient collateral hypoperfusion (tCHP), which was achieved by direct MCA ligation through craniotomy and 1-h bilateral common carotid artery occlusion at the beginning of pMCAO. The infusion of 20 ml/kg of 4 °C cold saline (CS) or 37 °C warm saline (WS) into the ipsilateral internal carotid artery (ICA) was performed for 15 min in intra- or post-tCHP. Neurological scores, infarct/edema volumes, and neuronal apoptosis and reactive gliosis were compared between the CS and WS groups and a non-infusion control group after 48 h of reperfusion. Although brain temperatures were only reduced by 2-3 °C for 15 min, the CS group had significantly better neurological scores, smaller infarct/edema volumes, and less penumbral neuronal apoptosis and reactive gliosis than the control and WS groups. The post-tCHP CS group exhibited prominent neuroprotective effects, even though infarct volumes and neuronal apoptosis were reduced less than those in the intra-tCHP CS group. In conclusion, we demonstrated the neuroprotective effects of transarterial regional hypothermia in an ischemic model of pMCAO with tCHP. Even though MCAO is persistent, cold infusion via the ICA is neuroprotective for the penumbra, suggesting the wider therapeutic application of this therapy.