Long-term mild hypothermia promotes neuroprotection by antagonizing the rebound of intracranial pressure after traumatic brain injury in rats

doi:10.11958/20231091

Abstract

Abstract:

Objective To explore the optimal duration of long-term mild hypothermia (MHT) for traumatic brain injury (TBI) in rats, and observe its effect on intracranial pressure (ICP) and neurological function. Methods Forty-eight healthy adult male SD rats were divided into the normal temperature treatment (NT) group, the MHT4 h group, the MHT24 h group and the MHT48 h group by random number table method, with twelve rats in each group. The TBI model of rats was prepared by electronic controllable cortical injury device, and ICP monitoring probe was implanted. After modeling, the NT group was treated with normal temperature (37 ℃), and the other groups were treated with low temperature (33.0±1.0 ) ℃ for 4 h, 24 h and 48 h, respectively. ICP was monitored and brain water content (BWC) was calculated after MHT treatment in each group. Blood-brain barrier permeability was determined by Evansland (EB) staining. The expression of 5-bromodeoxyuracil nucleoside (BrdU), neuronal nuclear antigen antibody (NeuN) and leukocyte differentiation antigen 86 (CD86) positive cells were detected by immunofluorescence staining. The expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), inducable nitric oxide synthase (iNOS), interleukin (IL) -10 and arginase 1 (Arg-1) were detected by Western blot assay. Results Compared with the NT group, levels of BWC, ICP, EB, and CD86 positive cells, Bax and iNOS expression levels were decreased in the MHT4 h group, the MHT24 h group and the MHT48 h group, and the number of BrdU positive cells and BrdU/NeuN double-labeled positive cells were increased in hippocampus. The expression levels of Bcl-2, IL-10 and Arg-1 were increased (P<0.01). Compared with the MHT24 h group, levels of BWC, ICP and EB, and CD86 positive cells, Bax and iNOS expression were decreased, and the number of BrdU positive cells and BrdU/NeuN double-labeled positive cells were increased in the MHT48 h group, while levels of Bcl-2, IL-10 and Arg-1 expression were increased (P<0.01). Conclusion Long-term MHT can promote the proliferation and differentiation of neurons, inhibit apoptosis and reduce inflammation by suppressing ICP rebound, further promoting neuroprotection after TBI.

Key words: craniocerebral trauma, intracranial pressure, hypothermia, induced, blood-brain barrier, mild hypothermia, long time horizon

CLC Number:

R651.1+5

Figures/Tables 9

References 19

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组别	BWC/%	ICP/mmHg
NT组	90.41±1.51	26.10±0.84
MHT4 h组	86.57±1.85^a	23.40±1.34^a
MHT24 h组	82.07±2.04^ab	18.50±0.92^ab
MHT48 h组	76.42±1.76^ac	11.40±0.98^ac
F	116.000^＊＊	347.900^＊＊

组别	BWC/%	ICP/mmHg
NT组	90.41±1.51	26.10±0.84
MHT4 h组	86.57±1.85^a	23.40±1.34^a
MHT24 h组	82.07±2.04^ab	18.50±0.92^ab
MHT48 h组	76.42±1.76^ac	11.40±0.98^ac
F	116.000^＊＊	347.900^＊＊

组别	BrdU	BrdU/NeuN	CD86
NT组	39.83±5.27	27.33±4.76	81.33±6.95
MHT4 h组	65.50±9.42^a	55.00±7.56^a	59.33±5.65^a
MHT24 h组	53.83±6.08^ab	44.50±4.63^ab	70.83±7.99^ab
MHT48 h组	76.17±8.61^ac	64.50±8.26^ac	48.83±8.23^ac
F	25.690^＊＊	35.860^＊＊	22.460^＊＊

组别	BrdU	BrdU/NeuN	CD86
NT组	39.83±5.27	27.33±4.76	81.33±6.95
MHT4 h组	65.50±9.42^a	55.00±7.56^a	59.33±5.65^a
MHT24 h组	53.83±6.08^ab	44.50±4.63^ab	70.83±7.99^ab
MHT48 h组	76.17±8.61^ac	64.50±8.26^ac	48.83±8.23^ac
F	25.690^＊＊	35.860^＊＊	22.460^＊＊

组别	Bcl-2	Bax
NT组	0.59±0.07	1.47±0.15
MHT4 h组	1.10±0.15^a	1.08±0.13^a
MHT24 h组	0.80±0.11^ab	0.80±0.10^ab
MHT48 h组	1.34±0.12^ac	0.49±0.15^ac
F	25.230^＊＊	29.820^＊＊