Hypothermia Induced by Oxcarbazepine after Transient Forebrain Ischemia Exerts Therapeutic Neuroprotection through Transient Receptor Potential Vanilloid Type 1 and 4 in Gerbils.

Abstract

In the present study, we investigated the neuroprotective effect of post-ischemic treatment with oxcarbazepine (OXC; an anticonvulsant compound) against ischemic injury induced by transient forebrain ischemia and its mechanisms in gerbils. Transient ischemia was induced in the forebrain by occlusion of both common carotid arteries for 5 min under normothermic conditions (37 ± 0.2 °C). The ischemic gerbils were treated with vehicle, hypothermia (whole-body cooling; 33.0 ± 0.2 °C), or 200 mg/kg OXC. Post-ischemic treatments with vehicle and hypothermia failed to attenuate and improve, respectively, ischemia-induced hyperactivity and cognitive impairment (decline in spatial and short-term memory). However, post-ischemic treatment with OXC significantly attenuated the hyperactivity and the cognitive impairment, showing that OXC treatment significantly reduced body temperature (to about 33 °C). When the hippocampus was histopathologically examined, pyramidal cells (principal neurons) were dead (lost) in the subfield Cornu Ammonis 1 (CA1) of the gerbils treated with vehicle and hypothermia on Day 4 after ischemia, but these cells were saved in the gerbils treated with OXC. In the gerbils treated with OXC after ischemia, the expression of transient receptor potential vanilloid type 1 (TRPV1; one of the transient receptor potential cation channels) was significantly increased in the CA1 region compared with that in the gerbils treated with vehicle and hypothermia. In brief, our results showed that OXC-induced hypothermia after transient forebrain ischemia effectively protected against ischemia-reperfusion injury through an increase in TRPV1 expression in the gerbil hippocampal CA1 region, indicating that TRPV1 is involved in OXC-induced hypothermia.

• Authors: Hyung-Il Kim, Jae-Chul Lee, Dae Won Kim, Myoung Cheol Shin, Jun Hwi Cho, Ji Hyeon Ahn, Soon-Sung Lim, Il Jun Kang, Joon Ha Park, Moo-Ho Won, Tae-Kyeong Lee
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 1 (Dec 27 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35008663 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents
• TRPV Cation Channels
• Oxcarbazepine

Topics

• Animals
• Body Temperature (drug effects)
• Cell Nucleus (drug effects, metabolism)
• Cognition (drug effects)
• Gerbillinae
• Hippocampus (drug effects, pathology)
• Hypothermia, Induced
• Ischemia (pathology, physiopathology, therapy)
• Male
• Neurons (drug effects, pathology)
• Neuroprotection (drug effects)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oxcarbazepine (pharmacology, therapeutic use)
• Prosencephalon (drug effects, pathology, physiopathology)
• TRPV Cation Channels (metabolism)