Chronic neurodegenerative consequences of traumatic brain injury

Chauhan, Neelima B.

doi:10.3233/rnn-130354

Cited by 80 publications

(71 citation statements)

References 346 publications

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“…Traumatic brain injury (TBI) occurs as a result of direct mechanical insult to the brain, and induces degeneration and death in the central nervous system (CNS) [1,2]. TBI is prevalent especially in male adolescents and adults, and severely affects the quality of peoples’ lives.…”

Section: Introductionmentioning

confidence: 99%

Co-grafting of neural stem cells with olfactory en sheathing cells promotes neuronal restoration in traumatic brain injury with an anti-inflammatory mechanism

Liu

Zou

Belegu

et al. 2014

J Neuroinflammation

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BackgroundWe sought to investigate the effects of co-grafting neural stem cells (NSCs) with olfactory ensheathing cells (OECs) on neurological behavior in rats subjected to traumatic brain injury (TBI) and explore underlying molecular mechanisms.MethodsTBI was established by percussion device made through a weight drop (50 g) from a 30 cm height. Cultured NSCs and OECs isolated from rats were labeled by Hoechst 33342 (blue) and chloromethyl-benzamidodialkyl carbocyanine (CM-Dil) (red), respectively. Then, NSCs and/or OECs, separately or combined, were transplanted into the area surrounding the injury site. Fourteen days after transplantation, neurological severity score (NSS) were recorded. The brain tissue was harvested and processed for immunocytochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reverse transcription-polymerase chain reaction (RT-PCR).ResultsSignificant neurological function improvement was observed in the three transplant groups, compared to the TBI group, and co-transplantation gave rise to the best improvement. Morphological evaluation showed that the number of neurons in cortex from combination implantation was more than for other groups (P <0.05); conversely, the number of apoptotic cells showed a significant decrease by TUNEL staining. Transplanted NSCs and OECs could survive and migrate in the brain, and the number of neurons differentiating from NSCs in the co-transplantation group was significantly greater than in the NSCs group. At the molecular level, the expressions of IL-6 and BAD in the co-graft group were found to be down regulated significantly, when compared to either the NSC or OEC alone groups.ConclusionThe present study demonstrates for the first time the optimal effects of co-grafting NSCs and OECs as a new strategy for the treatment of TBI via an anti-inflammation mechanism.

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Section: Introductionmentioning

confidence: 99%

Co-grafting of neural stem cells with olfactory en sheathing cells promotes neuronal restoration in traumatic brain injury with an anti-inflammatory mechanism

Liu

Zou

Belegu

et al. 2014

J Neuroinflammation

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“…CCI was induced by placing an electromagnetic stereotaxic impactor (a smooth blunt stainless-steal tip) (Leica Biosystems Richmond, formerly MyNeuroLab, Richmond, IL), perpendicular to the cortical surface and operating it at 1.0 mm depth and 3.0 m/s velocity (100 ms contact time) for 20 min. This protocol has been reported to produce mild TBI symptoms, such as, pain states, motor deficit, anxiety, and neurodegeneration [2, 13–15]. Then, the bone flap was sealed with a permanent cyanoacrylate-based fast-acting adhesive, and the skin was sutured.…”

Section: Methodsmentioning

confidence: 99%

“…But there are few satisfactory treatments available [2] because TBI patients have a wide-range of neurological manifestations, including chronic pain, mood disorders, sleep disturbance, and so on [1, 3], and underlying mechanisms of each remain unclear. Systematic clinical studies reveal that chronic pain is the major complaint in 51% of TBI patients [3, 4].…”

Section: Introductionmentioning

confidence: 99%

Tetramethylpyrazine attenuates periorbital allodynia and neuroinflammation in a model of traumatic brain injury

Wang

et al. 2017

J Inflamm

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BackgroundTraumatic brain injury (TBI) is a public health issue. As the major complaint in 51% of TBI patients, chronic pain is an important aspect in TBI treatment. Tetramethylpyrazine (TMP) is an important compound in Ligustrazine, an analgesic drug in traditional Chinese medicine, but its potential in relieving pain symptom in TBI has not been tested. We established a TBI mouse model with controlled cortical impact (CCI), and measured periorbital hypersensitivity with von Frey monofilaments. We examined activated microglia and astrocytes and the levels of substance P (SP) and inducible isoform of nitric oxide synthase (iNOS) with immunohistochemistry, measured mRNA and protein levels of proinflammatory cytokines with qPCR and enzyme-linked immunosorbent assay, respectively. Western blot was employed to detect molecules in NF-κB signaling pathway.ResultsTMP significantly attenuated periorbital hypersensitivity in TBI mice. Within 3 days after CCI, TMP attenuated activation of microglia and astrocytes, levels of SP, iNOS, and CGRP in trigeminal pathway, and levels of proinflammatory cytokines (including IL-6, TNF-α, IL-12). In isolated microglia, TMP attenuated the effects of lipopolysaccharide on the phosphorylation of cytoplasmic IKKα/β and IKB-α, and levels of nucleic p65.ConclusionTMP reversed periorbital hypersensitivity by limiting neuroinflammation at the primary stage of TBI, and could be a promising drug for pain treatment in TBI.

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“…A major medical and socio-economic problem, TBI is the leading cause of death in aged adults due to falls and in young adults due to war and accident from motor vehicles and sports (Chauhan, 2014). Other than critical care management, no currently approved therapies exist for TBI (Haddad and Arabi, 2012).…”

Section: Introductionmentioning

confidence: 99%

Targeting the nNOS/peroxynitrite/calpain system to confer neuroprotection and aid functional recovery in a mouse model of TBI

et al. 2016

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Traumatic brain injury (TBI) derails nitric oxide (NO)-based anti-inflammatory and anti-excitotoxicity mechanisms. NO is consumed by superoxide to form peroxynitrite, leading to decreased NO bioavailability for S-nitrosoglutathione (GSNO) synthesis and regulation of neuroprotective pathways. Neuronal peroxynitrite is implicated in neuronal loss and functional deficits following TBI. Using a contusion mouse model of TBI, we investigated mechanisms for the opposed roles of GSNO versus peroxynitrite for neuroprotection and functional recovery. TBI was induced by controlled cortical impact (CCI) in adult male mice. GSNO treatment at 2 h after CCI decreased the expression levels of phospho neuronal nitric oxide synthase (pnNOS), alpha II spectrin degraded products, and 3-NT, while also decreasing the activities of nNOS and calpains. Treatment of TBI with FeTPPS, a peroxynitrite scavenger, had effects similar to GSNO treatment. GSNO treatment of TBI also reduced neuronal degeneration and improved neurobehavioral function in a two-week TBI study. In a cell free system, SIN-1 (a peroxynitrite donor and 3-nitrotyrosinating agent) increased whereas GSNO (an S-nitrosylating agent) decreased calpain activity, and these activities were reversed by, respectively, FeTPPS and mercuric chloride, a cysteine-NO bond cleaving agent. These data indicate that peroxynitrite-mediated activation and GSNO-mediated inhibition of the deleterious nNOS/calpain system play critical roles in the pathobiology of neuronal protection and functional recovery in TBI disease. Given GSNO’s safety record in other diseases, its neuroprotective efficacy and promotion of functional recovery in this TBI study make low-dose GSNO a potential candidate for preclinical evaluation.

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Chronic neurodegenerative consequences of traumatic brain injury

Cited by 80 publications

References 346 publications

Co-grafting of neural stem cells with olfactory en sheathing cells promotes neuronal restoration in traumatic brain injury with an anti-inflammatory mechanism

Co-grafting of neural stem cells with olfactory en sheathing cells promotes neuronal restoration in traumatic brain injury with an anti-inflammatory mechanism

Tetramethylpyrazine attenuates periorbital allodynia and neuroinflammation in a model of traumatic brain injury

Targeting the nNOS/peroxynitrite/calpain system to confer neuroprotection and aid functional recovery in a mouse model of TBI

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