Transarterial regional hypothermia provides robust neuroprotection in a rat model of permanent middle cerebral artery occlusion with transient collateral hypoperfusion.
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 20ml/kg of 4°C cold saline (CS) or 37°C warm saline (WS) into the ipsilateral internal carotid artery (ICA) was performed for 15min 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 48h of reperfusion. Although brain temperatures were only reduced by 2-3°C for 15min, 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.
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Kota
K
Kurisu
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan. Electronic address: abumiya@med.hokudai.ac.jp.
Takeo
T
Abumiya
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Masaki
M
Ito
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Masayuki
M
Gekka
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Toshiya
T
Osanai
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Hideo
H
Shichinohe
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Naoki
N
Nakayama
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Ken
K
Kazumata
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Kiyohiro
K
Houkin
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001831:Body Temperature; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D007036:Hypothermia, Induced; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009474:Neurons / Q000473:pathology / Q000502:physiology; D000066829:Neuroprotection / Q000502:physiology; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000628:therapy
Apoptosis; Gliosis; Hypothermia; Partial reperfusion injury; Permanent middle cerebral artery occlusion; Transarterial regional hypothermia