Blocking Tumor Necrosis Factor-Alpha Expression Prevents Blast-Induced Excitatory/Inhibitory Synaptic Imbalance and Parvalbumin-Positive Interneuron Loss in the Hippocampus
| Autor: | Shaowen Bao, Alexander K. Zinsmaier, Jinsheng Zhang, Sungchil Yang, Tatiana A. Yatskievych, Weihua Wang, Ruizhu Lin, Ethan Firestone |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Interneuron Traumatic brain injury Hippocampus Neurological disorder Neurotransmission Inhibitory postsynaptic potential Synaptic Transmission Mice 03 medical and health sciences 0302 clinical medicine Blast Injuries Interneurons Brain Injuries Traumatic Animals Medicine biology Tumor Necrosis Factor-alpha business.industry medicine.disease Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Excitatory postsynaptic potential biology.protein Neurology (clinical) business Neuroscience 030217 neurology & neurosurgery Parvalbumin |
| Zdroj: | Journal of Neurotrauma. 35:2306-2316 |
| ISSN: | 1557-9042 0897-7151 |
| DOI: | 10.1089/neu.2018.5688 |
| Popis: | Traumatic brain injury (TBI) is a major cause of neurological disorder and death in civilian and military populations. It comprises two components-direct injury from the traumatic impact and secondary injury from ensuing neural inflammatory responses. Blocking tumor necrosis factor-alpha (TNF-α), a central regulator of neural inflammation, has been shown to improve functional recovery after TBI. However, the mechanisms underlying those therapeutic effects are still poorly understood. Here, we examined effects of 3,6'-dithiothalidomide (dTT), a potentially therapeutic TNF-α inhibitor, in mice with blast-induced TBI. We found that blast exposure resulted in elevated expression of TNF-α, activation of microglial cells, enhanced excitatory synaptic transmission, reduced inhibitory synaptic transmission, and a loss of parvalbumin-positive (PV+) inhibitory interneurons. Administration of dTT for 5 days after the blast exposure completely suppressed blast-induced increases in TNF-α transcription, largely reversed blasted-induced synaptic changes, and prevented PV+ neuron loss. However, blocking TNF-α expression by dTT failed to mitigate blast-induced microglial activation in the hippocampus, as evidenced by their non-ramified morphology. These results indicate that TNF-α plays a major role in modulating neuronal functions in blast-induced TBI and that it is a potential target for treatment of TBI-related brain disorders. |
| Databáze: | OpenAIRE |
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