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. 2022 Feb;13(1):132-141.
doi: 10.1007/s12975-021-00910-8. Epub 2021 Apr 24.

Targeted Temperature Management at 36 °C Shows Therapeutic Effectiveness via Alteration of Microglial Activation and Polarization After Ischemic Stroke

Jong Youl Kim  1 , Ju Hee Kim  2 , Joohyun Park  1 , Jin Ho Beom  2 , Sung Phil Chung  2 , Je Sung You  3 , Jong Eun Lee  4   5   6
Affiliations

Targeted Temperature Management at 36 °C Shows Therapeutic Effectiveness via Alteration of Microglial Activation and Polarization After Ischemic Stroke

Jong Youl Kim et al. Transl Stroke Res. 2022 Feb.

Abstract

Ischemic injury leads to cell death and inflammatory responses after stroke. Microglia especially play a crucial role in this brain inflammation. Targeted temperature management (TTM) at 33 °C has shown neuroprotective effects against many acute ischemic injuries. However, it has also shown some adverse effects in preclinical studies. Therefore, we explored the neuroprotective effect of TTM at 36 °C in the ischemic brain. To confirm the neuroprotective effects of hypothermia, mice were subjected to a permanent stroke and then treated with one of the TTM paradigms at 33 and 36 °C. For comparison of TTM at 33 and 36 °C, we examined neuronal cell death and inflammatory response, including activation and polarization of microglia in the ischemic brain. TTM at 33 and 36 °C showed neuroprotective effects in comparison with normal body temperature (NT) at 37.5 °C. Mice under TTM at 33 and 36 °C showed ~ 45-50% fewer TUNEL-positive cells than those under NT. In IVIS spectrum CT, the activation of microglia/macrophage in CX3CR1GFP mice reduced after TTM at 33 and 36 °C in comparison with that after NT on day 7 after ischemic stroke. The number of Tmem119-positive cells under TTM at 33 and 36 °C was ~ 45-50% lower than that in mice under NT. TTM at 33 and 36 °C also increased the ratio of CD206-/CD86-positive cells than the ratio of CD86-/CD206-positive cells by ~ 1.2-fold. Thus, TTM at 33 and 36 °C could equivalently decrease the expression of certain cytokines after ischemic stroke. Our study suggested that TTM at 33 or 36 °C produces equivalent neuroprotective effects by attenuating cell death and by altering microglial activation and polarization. Therefore, TTM at 36 °C can be considered for its safety and effectiveness in ischemic stroke.

Keywords: Cell death; Inflammation; Ischemic stroke; Microglia; Targeted temperature management.

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