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

Abstract

(248 words)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-hour 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 minutes in intraor 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 hours of reperfusion. Although brain temperatures were only reduced by 2-3°C for 15 minutes, 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.

Selective brain hypothermia ameliorates focal cerebral ischemia-reperfusion injury via inhibiting Fis1 in rats

“…SBH is more suitable for neuroprotection after stroke because it can quickly reach the target temperature and avoid the adverse effects associated with general hypothermia [37,38]. Moreover, transarterial regional hypothermia, which can achieve SBH, may exert strong neuroprotective effects in the MCAO with transient collateral hypoperfusion model [19]. In the present study, we prepared a hypothermia model following MCAO by perfusing cold saline through the ICA, and the results of cortical and rectal temperatures showed that SBH models were successfully established.…”

“…According to previously used successful parameters [19], 4 °C cold saline was infused (20 ml/kg) through the microcatheter placed in the right ICA via the external carotid artery for 15 min immediately after removal of the filament in the HT group. To eliminate the interference from hemodilution by saline infusion, we performed 37 °C warm saline infusion in the same manner in the NT group.…”

“…According to our previous study, general hypothermia-induced neuroprotective effects against cerebral I/R injury are associated with suppressing mitochondrial fission by inhibiting the translocation of Drp1 from the cytoplasm to mitochondria in mice [17]. However, compared with general hypothermia, selective brain hypothermia (SBH) is strongly expected to become a novel attractive treatment for ischemic stroke due to its rapid cooling action and fewer systemic side effects [18,19]. Unfortunately, whether SBH could alleviate I/R injury by inhibiting Fis1 is not well known.…”

Cofilin-actin rod formation in experimental stroke is attenuated by therapeutic hypothermia and overexpression of the inducible 70 kD inducible heat shock protein (Hsp70)

“…A focal cerebral infarct was induced by permanent occlusion of the left distal middle cerebral artery (dMCAO) as previously described. [21,22] Briefly, a small craniotomy was made above the proximal segment of the middle cerebral artery (MCA), and the MCA was exposed after the dura was opened and retracted. The MCA was occluded by coagulation at the MCA segment just proximal to the olfactory branch.…”

“…As the MCA border is assumed to be the farthest margin occupied by an infarction due to MCAO, the MCA border may be considered the area where the ischemic region may be spared with a suitable neuroprotective treatment; the MCA border was anatomically defined as constant regions at 1.8 and 3.6 mm lateral from the midline, within the cortex corresponding to the edge of the brain supplied by the MCA. [21,29] The "ischemic core" was defined as the center of the ischemic lesion, well within the boundaries of the infarct. The "ischemic borderzone" was defined as the region immediately adjacent to the ischemic lesion, [15] as visually delineated by NeuN and DAPI staining.…”