Neurointerventional infusion of hemoglobin oxygen carrier prevents brain damage from acute cerebral ischemia in rats

Hong Gao; Han Peng; Hua Yang; Qiuping Li; Xin Xiang

doi:10.3389/fsurg.2023.1050935

Neurointerventional infusion of hemoglobin oxygen carrier prevents brain damage from acute cerebral ischemia in rats

Front Surg. 2023 Mar 3:10:1050935. doi: 10.3389/fsurg.2023.1050935. eCollection 2023.

Authors

Hong Gao¹, Han Peng², Hua Yang², Qiuping Li¹, Xin Xiang²

Affiliations

¹ Department of Neurosurgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China.
² Department of Neurosurgery, Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Abstract

Aim: To save brain cells in acute cerebral infarction by injecting hemoglobin oxygen carrier (HBOC) into the blood vessel blockage of the cerebral infarction site through a microcatheter.

Methods: 120 male rats were divided into four groups: control (CTRL), ischemia (I), ischemia + low perfusion (I + LP), and ischemia + high perfusion (I + HP). Perfusion groups (ischemia, I + LP, and I + HP) underwent MCAO surgery with intraluminal monofilament. These groups were subdivided into 6 h, 12 h, and 24 h (n = 10/group). RT-PCR, Western-Blot, immunohistochemistry, and apoptosis assays were used to detect apoptosis, hypoxia range and extent, and ischemia.

Results: Compared with the I group, the neurological deficit sign scores of the I + HP group were statistically significant at 12 h. Compared with the I group, the neurological deficit sign scores of the I + LP group and the I + HP group were statistically significant at 24 h. At all time points, compared with the I group and the I + LP group, Caspase-3, HIF-1α, and Cytochrome C protein levels were significantly decreased in the I + HP group. Bcl-2 and BAX mRNA levels were also significantly decreased in the same group. TNF-α, IL-6, and IL-1β cytokines were significantly decreased in the I + HP group as well. The infarct size of rats in the I + HP group was smaller than that of the I + LP group, which was smaller than ischemia alone. Time of perfusion had an obvious effect as infarct size was smaller with longer perfusion. The number of Nissl stained cells in the I + HP group was increased compared with the ischemia and the I + LP group, and was proportional to the time of perfusion.

Conclusion: Time- and rate-controlled perfusion of HBOC to acutely occluded cerebral vascular regions through microcatheters can effectively protect ischemic brain tissue in rats.

Keywords: acute cerebral ischemia; hemoglobin oxygen carrier (HBOC); microcatheter perfusion; neurointervention; rats.

Grants and funding

We thank the support from 2016 Natural Science Foundation of China Number: 81660239 and 2020 Xiamen Medical and Health Guidance Project Number: 3502Z20209052.