Inflammatory cytokines are involved in dihydrocapsaicin (DHC) and regional cooling infusion (RCI)-induced neuroprotection in ischemic rat.

Abstract

OBJECTIVE:

The combination of pharmacological hypothermia - dihydrocapsaicin (DHC) and intra-arterial regional cooling infusions (RCI) was found to enhance the efficiency of hypothermia and efficacy of hypothermia-induced neuroprotection in acute ischemic stroke. The aim of this study was to explore whether the combination could induce a long-term neuroprotective effects, as well as the underlying mechanism.

METHODS:

Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h using intraluminal hollow filament. The ischemic rats were randomized to receive pharmacological hypothermia by intraperitoneal (i.p.) injection of DHC, physical hypothermia by RCI of 6 ml cold saline (4 °C), the combination, and no treatment. Over a 21-day period, brain damage was determined by infarct volume with MRI, and neurological deficit with grid-walking and beam balance tests. Blood brain barrier (BBB) was assessed by Evans-Blue (EB) contents. Inflammatory cytokines were determined in peri-infarct area by antibody array and ELISA.

RESULTS:

The combination of DHC and RCI reduced (p < 0.05) infarct volume and neurologic deficit after stroke. BBB leakage and pro-inflammatory cytokines (IFN-γ, IL-2, and TNF-α) were significantly decreased (p < 0.05) because of the combination, while protective cytokines (IL-4 and IL-10) were increased (p < 0.05) in the peri-infarct area.

CONCLUSIONS:

The combination approach enhanced the efficacy of hypothermia-induced neuroprotection following ischemic stroke. Our findings provide a hint to translate the combination method from bench to bedside.

• Authors: Di Wu, Xinglong Zhi, Yunxia Duan, Mo Zhang, Hong An, Wenjing Wei, Kai Dong, Ying Zhang, Jingfei Shi, Xiaoduo He, Jun Zhang, Chuanjie Wu, Ran Meng, Yuchuan Ding, Xunming Ji
• Journal: Brain research (Brain Res) Vol. 1710 Pg. 173-180 (05 01 2019) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 30584925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• Neuroprotective Agents
• Capsaicin
• dihydrocapsaicin

Topics

• Animals
• Blood-Brain Barrier
• Brain Injuries (drug therapy)
• Brain Ischemia (drug therapy, metabolism)
• Capsaicin (analogs & derivatives, metabolism, pharmacology)
• Cytokines
• Hypothermia (drug therapy)
• Hypothermia, Induced (methods)
• Infarction, Middle Cerebral Artery (drug therapy)
• Infusions, Intra-Arterial (methods)
• Ischemic Attack, Transient (drug therapy)
• Male
• Neuroprotection (drug effects)
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy)
• Stroke (drug therapy)