The Role of BDNF in Experimental and Clinical Traumatic Brain Injury

Gustafsson, David; Klang, Andrea; Thams, Sebastian; Rostami, Elham

doi:10.3390/ijms22073582

Cited by 54 publications

(34 citation statements)

References 151 publications

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“…Inflammatory biomarkers were chosen to investigate chronic inflammation related to psychological and brain trauma. Brain derived neurotropic factor (BDNF) was chosen based on its association with brain injury both in regulating neurodegeneration and neural protection [10][11][12] and in recovery [13,14]. We hypothesized that close blast exposure and mTBI would be related to increases in pro-inflammatory markers, as measured by IL-6, TNFα, and eotaxin-1, and decreases in antiinflammatory markers, such as interleukin-10 (IL-10).…”

Section: Introductionmentioning

confidence: 99%

Plasma biomarkers associated with deployment trauma and its consequences in post-9/11 era veterans: initial findings from the TRACTS longitudinal cohort

et al. 2022

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Mild traumatic brain injury (mTBI) is among the most common injuries sustained by post-9/11 veterans; however, these injuries often occur within the context of psychological trauma. Blast exposure, even in the absence of a diagnosable TBI, leads to changes in neural connectivity and congitive functioning. Therefore, considering clinical comorbidities and injury characteristics is critical to understanding the long-term effects of mTBI. Research is moving towards identifying diagnostic and prognostic blood-based biomarkers for TBI; however, few studies include other prevalent clinical and medical comorbidities related to deployment. Here, we present the initial cross-sectional relationships between plasma biomarkers, clinical, and medical comorbidities in a well-characterized longitudinal sample of 550 post-9/11 veteran men and women. We examined biomarkers associated with inflammation (interleukin 6 and 10, tumor necrosis factor α, and eotaxin) and neurodegeneration (neurofilament light, glial fibrillary acidic protein (GFAP), tau, brain derived neurotrophic factor, amyloid ß 40 and 42, phosphorylated neurofilament heavy chain, and neuron specific enolase). Univariate analyses of covariance (ANCOVA) were conducted to determine mean level differences between close blast (blasts that occur within 0–10 meters) and mTBI groups. Our primary findings were twofold: (1) Inflammatory markers were consistently higher in participants exposed to close blasts and were strongly related to deployment-related psychopathology. (2) GFAP was consistently lower in participants exposed to blast and mTBI and lower GFAP was associated with more severe psychological symptoms. More research is clearly needed; however, our findings indicate that chronic increased inflammation and decreased GFAP may be related to close blast exposure.

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Section: Introductionmentioning

confidence: 99%

Plasma biomarkers associated with deployment trauma and its consequences in post-9/11 era veterans: initial findings from the TRACTS longitudinal cohort

et al. 2022

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“…BDNF is expressed by neurons, astrocytes and various immune cells. BDNF protects neurons and supports OPC proliferation in traumatically injured nerve tissues ( 45 ). We observed that BDNF from neurons attenuated EAE symptoms, in agreement with a previous study ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Treatment With CD52 Antibody Protects Neurons in Experimental Autoimmune Encephalomyelitis Mice During the Recovering Phase

et al. 2021

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Multiple sclerosis (MS) is a chronic autoimmune disease driven by T and B lymphocytes. The remyelination failure and neurodegeneration results in permanent clinical disability in MS patients. A desirable therapy should not only modulate the immune system, but also promote neuroprotection and remyelination. To investigate the neuroprotective effect of CD52 antibody in MS, both C57BL/6J and SJL mice with experimental autoimmune encephalomyelitis (EAE) were treated with CD52 antibody at the peak of disease. Treatment with CD52 antibody depleted T but not B lymphocytes in the blood, reduced the infiltration of T lymphocytes and microglia/macrophages in the spinal cord. Anti-CD52 therapy attenuated EAE scores during the recovery phase. It protected neurons immediately after treatment (within 4 days) as shown by reducing the accumulation of amyloid precursor proteins. It potentially promoted remyelination as it increased the number of olig2/CC-1-positive mature oligodendrocytes and prevented myelin loss in the following days (e.g., 14 days post treatment). In further experiments, EAE mice with a conditional knockout of BDNF in neurons were administered with CD52 antibodies. Neuronal deficiency of BDNF attenuated the effect of anti-CD52 treatment on reducing EAE scores and inflammatory infiltration but did not affect anti-CD52 treatment-induced improvement of myelin coverage in the spinal cord. In summary, anti-CD52 therapy depletes CD4-positive T lymphocytes, prevents myelin loss and protects neurons in EAE mice. Neuronal BDNF regulates neuroprotective and anti-inflammatory effect of CD52 antibody in EAE mice.

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“…The coordination of the BDNF and TrkB receptors governs a wide range of neural activities, including neuronal survival, differentiation, migration, axonal sprouting, synaptogenesis, plasticity, and the enhancement of long-term potentiation (LTP), which influences learning and memory [86][87][88]. Growing studies focusing on BDNF have emerged, but there are discrepancies among the results of BDNF expression at different post-injury times, regions in the CNS, genetic polymorphisms, and clinical outcomes [89][90][91].…”

Section: Brain-derived Neurotrophic Factormentioning

confidence: 99%

“…The BDNF protein possesses a single-nucleotide polymorphism (SNP) site at rs6265, at the 66-amino acid position, which results in the replacement of wildtype Val with Met (Val66Met, valine to methionine) [92]. Although other SNPs of BDNF such as rs71244, rs1519480, and rs1153659 have been reported to influence the outcome after TBI, the most studied polymorphism of BDNF in humans is rs6265 (Val66Met) [89]. The frequency of the Met66 allele is approximately 25-32% in Caucasian populations and 40-50% in Asian populations [93].…”

Section: Single-nucleotide Polymorphism Of Bdnfmentioning

confidence: 99%

The Roles of Neurotrophins in Traumatic Brain Injury

Lin

Kuo

Luh

2021

Life

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Neurotrophins are a collection of structurally and functionally related proteins. They play important roles in many aspects of neural development, survival, and plasticity. Traumatic brain injury (TBI) leads to different levels of central nervous tissue destruction and cellular repair through various compensatory mechanisms promoted by the injured brain. Many studies have shown that neurotrophins are key modulators of neuroinflammation, apoptosis, blood–brain barrier permeability, memory capacity, and neurite regeneration. The expression of neurotrophins following TBI is affected by the severity of injury, genetic polymorphism, and different post-traumatic time points. Emerging research is focused on the potential therapeutic applications of neurotrophins in managing TBI. We conducted a comprehensive review by organizing the studies that demonstrate the role of neurotrophins in the management of TBI.

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The Role of BDNF in Experimental and Clinical Traumatic Brain Injury

Cited by 54 publications

References 151 publications

Plasma biomarkers associated with deployment trauma and its consequences in post-9/11 era veterans: initial findings from the TRACTS longitudinal cohort

Plasma biomarkers associated with deployment trauma and its consequences in post-9/11 era veterans: initial findings from the TRACTS longitudinal cohort

Treatment With CD52 Antibody Protects Neurons in Experimental Autoimmune Encephalomyelitis Mice During the Recovering Phase

The Roles of Neurotrophins in Traumatic Brain Injury

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