myelin-basic-protein and Brain-Concussion

Mild traumatic brain injury (mTBI) is a common occurrence, with over 3 million cases reported every year in the United States. While research into the underlying pathophysiology is ongoing, there is an urgent need for better clinical guidelines that allow more consistent diagnosis of mTBI and ensure safe return-to-play timelines for athletes, nonathletes, and military personnel. The development of a suite of biomarkers that indicate the pathogenicity of mTBI could lead to clinically useful tools for establishing both diagnosis and prognosis. Here, we review the current evidence for mTBI biomarkers derived from investigations of the multifactorial pathology of mTBI. While the current literature lacks the scope and size for clarification of these biomarkers' clinical utility, early studies have identified some promising candidates.

Topics: Albumins; Apolipoproteins E; Biomarkers; Brain Concussion; Brain-Derived Neurotrophic Factor; Diffuse Axonal Injury; Genetic Markers; Glial Fibrillary Acidic Protein; Humans; Intermediate Filaments; Lipocalin-2; Military Personnel; Myelin Basic Protein; Phosphopyruvate Hydratase; Prion Proteins; Prognosis; S100 Calcium Binding Protein beta Subunit; Serum Albumin; Tight Junction Proteins; Ubiquitin Thiolesterase; United States

Repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions) is common and results in significant cognitive impairment, white matter injury and increased risk of neurodegeneration. Targeted therapies for rmTBI are lacking, though evidence from other injury models indicates that targeting N-methyl-d-aspartate (NMDA) receptor (NMDAR)-mediated glutamatergic toxicity might mitigate rmTBI-induced injury. We have previously shown that the NMDAR antagonist memantine lessens axonal injury and restores long term potentiation after rmTBI. Here, we evaluated whether the protective effects of memantine include oligodendrocyte specific mechanisms, as prior studies suggest that oligodendrocytes are particularly vulnerable to glutamatergic toxicity. Mice were subjected to rmTBI injury (5 injuries in 5 days) and randomized to treatment with memantine or with vehicle (n = 32/group). At the molecular level, oligodendrocyte counts and function (myelin basic protein, MBP) were assessed by immunohistochemistry and western blot at days 3, 7 and 28 days after the last injury. Axon integrity was assessed by neurofilament light chain (NF-l) expression and axonal ultrastructure was evaluated by electron microscopy. Compared to vehicle-treated mice, memantine-treated mice were protected against oligodendrocyte loss and decreased MBP expression at subacute time points after injury. Memantine treatment also protected against axon damage assessed by NF-l expression. These data suggest that the therapeutic effects of post-concussive NMDAR antagonism may in part work through oligodendrocyte specific mechanisms, which may have implications for long term neurodegenerative sequelae after multiple concussions.

Topics: Animals; Axons; Brain; Brain Concussion; Glycogen Synthase Kinase 3 beta; Male; Memantine; Mice; Mice, Inbred C57BL; Models, Animal; Myelin Basic Protein; Neurofilament Proteins; Oligodendroglia; Receptors, N-Methyl-D-Aspartate

Serum levels of myelin basic protein (MBP) were measured in 112 patients after acute head injury by enzyme linked immuno-absorbent assay (ELISA). Patients with cerebral concussion showed no significant change in serum MBP. Patients with cerebral contusion, extradural hematoma or intracerebral hematoma had a mean serum MBP concentration much higher than that of patients with cerebral concussion. And patients with extradural hematoma had a mean serum MBP concentration much lower than that of patients with cerebral contusion and intracerebral hematoma; the differences were significant (P < 0.05). But there was no significant difference between patients with cerebral contusion and intracerebral hematoma (P > 0.05). The amount of serum MBP was significantly correlated with the volume of extradural hematoma, intracerebral hematoma and with the extent of the cerebral contusion (P < 0.05). This study suggested that the serum MBP may reflect the type and severity of closed head injury patients.

Topics: Adolescent; Adult; Aged; Brain Concussion; Cerebral Hemorrhage; Child; Enzyme-Linked Immunosorbent Assay; Female; Hematoma; Humans; Male; Middle Aged; Myelin Basic Protein; Trauma Severity Indices

Data are reported on the content of neurospecific proteins in the blood serum of 87 patients with closed head injuries. It has been established that the method of competent EIA can be used for measuring the content of neurospecific proteins. It has also been shown that their content in the blood depended on the severity of injury: the more severe injury the higher the protein content. Some aspects have been revealed of the blood content of protein 14-3-2 and total myelin protein. The authors discuss a possible diagnostic importance of these proteins in the differential diagnosis of the severity of closed head injuries and in the determination of lesions of the neuroglia and neurons both in mild and grave trauma.

Topics: Biomarkers; Brain Concussion; Head Injuries, Closed; Humans; Immunoenzyme Techniques; Myelin Basic Protein; Nerve Tissue Proteins; Oligodendroglia; Time Factors

Immune disorders characteristic of the late period of craniocerebral trauma involve T-cellular, regulatory link and were represented by a reduction of T-cells count and function with disbalance in lymphocytes-helpers, increase in macrophagal and lymphoid suppressors activity susceptible to indomethacin++. The changes also include the neurosensibilization of cellular and humoral type to brain-specific++ proteins: OBM, 14-3-2, S-100. Most pronounced changes were detected in patients after severe brain concussion with focal neural changes persisting in the late period.

Topics: Adult; Autoantigens; Brain Concussion; Humans; Immunity; Immunoglobulins; Leukocyte Count; Lymphocyte Activation; Middle Aged; Myelin Basic Protein; Rosette Formation; T-Lymphocytes; Time Factors

We previously reported that the thymolysis was observed in acute experimental allergic encephalomyelitis (EAE) rats immunized with brain tissue homogenates in complete Freund adjuvant. This observation has led us to suppose that the central nervous system (CNS) has high antigenicity for self. To keep from the high antigenicity of CNS, the blood brain barrier (BBB) and cerebrospinal fluid (CSF) which maintain CNS in isolated state are essential for self. If the BBB is destroyed and brain tissue is disseminated in CSF, is oneself sensitized by CNS? In this experiment, we produced cerebral contusion in rats and the BBB was partially destroyed and brain tissue was disseminated in CSF. No clinical signs of EAE were observed by cerebral contusion was exposed to encephalitogen one week later, EAE was remarkably suppressed compared with those in controls or sham operated groups (p less than 0.001). Almost 80% of the rats with cerebral contusion showed no response to EAE. These results seen to show that self is sensitized by autologous brain tissue and CNS has high antigenicity.

Topics: Acute Disease; Animals; Autoantigens; Blood-Brain Barrier; Brain Concussion; Encephalomyelitis, Autoimmune, Experimental; Immune Tolerance; Myelin Basic Protein; Rats; Rats, Inbred Lew; Spinal Cord

Topics: Adolescent; Adult; Autoantibodies; Brain Concussion; Female; Humans; Male; Middle Aged; Myelin Basic Protein