Therapeutic treatment with vitamin C reduces focal cerebral ischemia-induced brain infarction in rats by attenuating disruptions of blood brain barrier and cerebral neuronal apoptosis

Free Radic Biol Med. 2020 Aug 1:155:29-36. doi: 10.1016/j.freeradbiomed.2020.05.015. Epub 2020 May 23.

Abstract

Stroke is a major public health problem and ranks third most common cause of death in adults worldwide. Thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy are the main revascularization therapies for acute ischemic stroke. However, ischemia-reperfusion injury, mainly caused by oxidative/nitrosative stress injury, after revascularization therapy can result in worsening outcomes. For better clinical prognosis, more and more studies have focused on the pharmaceutical neuroprotective therapies against free radical damage. The impact of vitamin C (ascorbic acid) on oxidative stress-related diseases is moderate because of its limited oral bioavailability and rapid clearance. However, recent evidence of the clinical benefit of parenteral vitamin C administration has emerged, especially in critical care. In this study we demonstrated that parenteral administration of vitamin C significantly improved neurological deficits and reduced brain infarction and brain edema by attenuating the transient middle cerebral artery occlusion (tMCAO)-induced nitrosative stress, inflammatory responses, and the resultant disruptions of blood brain barrier and cerebral neuronal apoptosis. These results suggest that parenteral administration of vitamin C has potential as an adjuvant agent with intravenous thrombolysis or endovascular thrombectomy in acute treatment of ischemic stroke.

Keywords: Blood brain barrier; Focal cerebral ischemia; Oxidative stress; Vitamin C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Ascorbic Acid / pharmacology
  • Blood-Brain Barrier
  • Brain
  • Brain Ischemia* / drug therapy
  • Infarction, Middle Cerebral Artery / drug therapy
  • Neuroprotective Agents* / pharmacology
  • Rats
  • Stroke*
  • Tissue Plasminogen Activator

Substances

  • Neuroprotective Agents
  • Tissue Plasminogen Activator
  • Ascorbic Acid