Perspectives on benefit of early and prereperfusion hypothermia by pharmacological approach in stroke

Fengwu Li; Jie Gao; Wesley Kohls; Xiaokun Geng; Yuchuan Ding

doi:10.4103/bc.bc_27_22

Perspectives on benefit of early and prereperfusion hypothermia by pharmacological approach in stroke

Brain Circ. 2022 Jun 30;8(2):69-75. doi: 10.4103/bc.bc_27_22. eCollection 2022 Apr-Jun.

Authors

Fengwu Li¹, Jie Gao¹, Wesley Kohls², Xiaokun Geng^{1

2

3}, Yuchuan Ding²

Affiliations

¹ Department of Neurology, Luhe Hospital, Capital Medical University, Beijing, China.
² Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
³ Department of Neurology, China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University, Beijing, China.

Abstract

Stroke kills or disables approximately 15 million people worldwide each year. It is the leading cause of brain injury, resulting in persistent neurological deficits and profound physical handicaps. In spite of over 100 clinical trials, stroke treatment modalities are limited in applicability and efficacy, and therefore, identification of new therapeutic modalities is required to combat this growing problem. Poststroke oxidative damage and lactic acidosis are widely-recognized forms of brain ischemia/reperfusion injury. However, treatments directed at these injury mechanisms have not been effective. In this review, we offer a novel approach combining these well-established damage mechanisms with new insights into brain glucose handling. Specifically, emerging evidence of brain gluconeogenesis provides a missing link for understanding oxidative injury and lactate toxicity after ischemia. Therefore, dysfunctional gluconeogenesis may substantially contribute to oxidative and lactate damage. We further review that hypothermia initiated early in ischemia and before reperfusion may ameliorate gluconeogenic dysfunction and subsequently provide an important mechanism of hypothermic protection. We will focus on the efficacy of pharmacologically assisted hypothermia and suggest a combination that minimizes side effects. Together, this study will advance our knowledge of basic mechanisms of ischemic damage and apply this knowledge to develop new therapeutic strategies that are desperately needed in the clinical treatment of stroke.

Keywords: Gluconeogenesis; PCK; ischemic stroke; neuroprotection; pharmacological hypothermia.

Publication types

Review