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1.
Neuroscience ; 522: 57-68, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37164305

RESUMO

Repeated mild traumatic brain injury (rTBI), one of the most common forms of traumatic brain injury, is a worldwide severe public health concern. rTBI induces cumulative neuronal injury, neurological dysfunction, and cognitive deficits. Although there are clinical treatment methods, there is still an urgent need to develop preventive approaches for susceptible populations. Using a repeated closed head injury (rCHI) rat model, we interrogate the effect of sub-lethal hyperthermia preconditioning (SHP) on rCHI-induced neuronal injury and behavioral changes. Our study applied the repeated weight-drop model to induce the rCHI. According to the changes of heat shock protein 70 (HSP 70) in the cortex and hippocampus following a single SHP treatment in normal rats, the SHP was delivered to the rats 18 h before rCHI. We found that HSP significantly alleviated rCHI-induced anxiety-like behaviors and impairments in motor abilities and spatial memory. SHP exerts significant neuroprotection against rCHI-induced neuronal damage, apoptosis, and neuroinflammation. Our findings support the potential use of SHP as a preventative approach for alleviating rCHI-induced brain damage.


Assuntos
Concussão Encefálica , Lesões Encefálicas , Traumatismos Cranianos Fechados , Hipertermia Induzida , Fármacos Neuroprotetores , Ratos , Animais , Fármacos Neuroprotetores/farmacologia , Modelos Animais de Doenças
2.
Brain Res ; 1772: 147665, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34562473

RESUMO

DHED (10ß,17ß-dihydroxyestra-1,4-dien-3-one) is a brain-selective prodrug of 17ß-estradiol and has been reported to have a strong neuroprotective effect. In this study, the exhaustive swimming rat model was used to investigate the therapeutic effects and mechanisms of intranasal DHED treatment. Male eight-week-old healthy Sprague Dawley rats were randomly divided into three groups: control group (Cont), exhaustive swimming (ES), and DHED + exhaustive swimming (DHED). The open-field test and beam-walking test were performed to measure exploratory behavior and general activity in rats. Immunofluorescence staining, western blotting, ELISA analysis and related assay kits were applied to measure brain damage, inflammatory cytokines, and apoptosis pathways. Behavioral data shows that DHED intranasal administration can prevent neurobehavioral impairment caused by exhaustive swimming. Using a series of bioanalytical assays, we demonstrated that DHED markedly abated neuronal injury compared to the exhaustive swimming group, as evidenced by the reduced expression of apoptosis-regulated proteins, the improvement of neural survival, and the prevention of myelin loss. In addition, mitochondrial fission was attenuated distinctly, and a dynamic equilibrium was restored. Intranasal administration of DHED likewise significantly suppressed reactive gliosis and the release of inflammatory cytokines in the rat cerebral motor cortex. Consistent with previous reports, DHED treatment ameliorated changes of excitatory neurotransmitters. These results provide strong support for the promising therapeutic effects of DHED on neuroprotection during exhaustive swimming. The underlying mechanisms may rely on mitochondrial dynamics, neuroinflammation, and the balance of neurotransmitters.


Assuntos
Androstenodióis/administração & dosagem , Androstenodióis/uso terapêutico , Lesões Encefálicas/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Condicionamento Físico Animal/efeitos adversos , Administração Intranasal , Animais , Apoptose/efeitos dos fármacos , Lesões Encefálicas/etiologia , Citocinas/metabolismo , Comportamento Exploratório , Masculino , Atividade Motora/efeitos dos fármacos , Doenças Neuroinflamatórias , Ratos , Ratos Sprague-Dawley , Natação
3.
Neurochem Int ; 142: 104926, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33276022

RESUMO

Major depressive disorder (MDD) is a prevalent psychiatric disorder that brings great harm and burden to both patients and society. This study aimed to examine the effects of whole-body vibration (WBV) training on a chronic restraint stress (CRS) induced depression rat model and provide an initial understanding of related molecular mechanisms. Adult Sprague-Dawley male rats were randomly divided into the following three groups: a) control group, b) depressive disorder group, and c) depression with WBV training treatment group. Daily food intake, body weight, sucrose preference test, open field test, elevated plus maze, forced swimming test, and Barnes maze task tests were performed. Immunofluorescence staining and ELISA analysis were used to assess neuronal damage, synaptic proteins, glial cells, and trophic factors. The data of behavioral tests and related biochemical indicators were statistically analyzed and compared between groups. Rats undergoing CRS showed increased anxiety-like behavior and memory impairment, along with synaptic atrophy and neuronal degeneration. WBV could reverse behavioral dysfunction, inhibit the degeneration of neurons, alleviate the damage of neurons and the pathological changes of glial cells, enhance trophic factor expression, and ameliorate the downregulation of dendritic and synaptic proteins after CRS. The effect of WBV in rats may be mediated via the reduction of hippocampal neuronal degeneration and by improving expression of synaptic proteins. WBV training exerts multifactorial benefits on MDD that supports its use as a promising new therapeutic option for improving depression-like behaviors in the depressive and/or potentially depressive.


Assuntos
Depressão/terapia , Restrição Física/efeitos adversos , Estresse Psicológico/terapia , Vibração/uso terapêutico , Animais , Depressão/metabolismo , Depressão/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia
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