Mild Brain Research Articles

IFN-β Deficiency Results in Fatal or Demyelinating Disease in C57BL/6 Mice Infected With Theiler’s Murine Encephalomyelitis Viruses

Type I Interferons (IFN-I) are important inducers of the antiviral immune response and immune modulators. IFN-β is the most highly expressed IFN-I in the central nervous system (CNS). The infection of SJL mice with the BeAn or the DA strain of Theiler’s murine encephalomyelitis virus (TMEV) results in a progressive demyelinating disease. C57BL/6 mice are usually resistant to TMEV-induced demyelination and eliminate these strains from the CNS within several weeks. Using C57BL/6 IFN-β knockout (IFN-β-/-) mice infected with TMEV, we evaluated the role of IFN-β in neuroinfection. Despite the resistance of C57BL/6 wild type (WT) mice to TMEV infection, DA-infected IFN-β-/- mice had to be killed at 7 to 8 days post infection (dpi) due to severe clinical disease. In contrast, BeAn-infected IFN-β-/- mice survived until 98 dpi. Nevertheless at 14 dpi, BeAn-infected IFN-β-/- mice showed a stronger encephalitis and astrogliosis, higher viral load as well as higher mRNA levels of Isg15, Eif2ak2 (PKR), Tnfa, Il1b, Il10, Il12 and Ifng in the cerebrum than BeAn-infected WT mice. Moreover, the majority of IFN-β-/- mice did not clear the virus from the CNS and developed mild demyelination in the spinal cord at 98 dpi, whereas virus and lesions were absent in the spinal cord of WT mice. Persistently infected IFN-β-/- mice also had higher Isg15, Eif2ak1, Tnfa, Il1a, Il1b and Ifng mRNA levels in the spinal cord at 98 dpi than their virus-negative counterparts indicating an activation of IFN-I signaling and ongoing inflammation. Most importantly, BeAn-infected NesCre+/- IFN-βfl/fl mice, which do not express IFN-β in neurons, astrocytes and oligodendrocytes, only developed mild brain lesions similar to WT mice. Consequently, IFN-β produced by neuroectodermal cells does not seem to play a critical role in the resistance of C57BL/6 mice against fatal and demyelinating disease induced by TMEV strains.

Dynamics of psychovegetative disorders in participants in modern wars

Twenty modem war participants who have had a mild brain trauma in Afganistan war were engaged in 7,000,30 year follow-up study. The basic vegetative state, regulatory brain system function, emotional state (MMPY, Scmiscek-Litman test, Spilberger questionnaire) were investigated in the follow-up study. The increase of nonspecific brain structure dysfunction clinical characteristics: suchas vegetative dysfunction with elevation of sympathetic activity and emotional shift to depressive and hypochondric disturbances was found.

ANALYSIS OF TRAUMATIC BRAIN INJURY: AND CORRELATION BETWEEN NCCT FINDINGS AND GCS ASSESSMENT

Introduction: TBI is one of the primary causes of disability, illness, and death in people of all ages all over the world. In addition to clinical evaluation by the Glasgow Coma Score (GCS), cerebral abnormalities in these individuals can be found early by computed tomography (CT), which is still the primary study of choice in the majority of TBI cases. Aims and Objectives: The purpose of this study was to see if the Glasgow coma scale and CT findings in individuals with head trauma correlated. Material and Methods: After receiving ethical committee clearance, prospective research was undertaken for a period of one year in a tertiary care hospital in North India. The Glasgow coma score was applied to 77 TBI cases, and computed tomography was conducted on all of them, with the results recorded. IBM Corp.'s SPSS statistics for Windows, was used to analyse the data. Results: Head trauma was most prevalent in people aged 26 to 35. (27.2 percent). The average age was 40.97 14.09 years, with a standard deviation of 14.09 years. Males made up the majority of the patients (83.1 percent). Road traffic accidents were the most prevalent cause of head injuries (84.4 percent). Half of the patients evaluated (50.6 percent) had severe head damage, followed by moderate (33.7 percent) and mild (15.5 percent) brain injury, according to GCS score. Intracranial haemorrhages were observed in 55 (71.42 percent) CT images, making them the most prevalent single or multiple lesions finding. In 45 (61%) of the patients, skull fractures were discovered. Midline shift was seen in 25 instances, with 18 individuals with serious head injuries having a midline displacement of less than 5mm. Patients with a low GCS had more CT results than those with a high GCS. The mean GCS score of individuals with a single lesion (11.3 1.99) differed significantly from the mean GCS of patients with multiple lesions (8.92 2.45). Conclusions: The degree of head damages as measured by the Glasgow coma scale and CT findings in individuals with head trauma were shown to be positively correlated in our study.

Neuroprotective Effects of Purpurin Against Ischemic Damage via MAPKs, Bax, and Oxidative Stress Cascades in the Gerbil Hippocampus

Purpurin has various effects, including anti-inflammatory effects, and can efficiently cross the blood–brain barrier. In the present study, we investigated the effects of purpurin on oxidative stress in HT22 cells and mild brain damage in the gerbil hippocampal CA1 region induced by transient forebrain ischemia. Oxidative stress induced by H2O2 was significantly ameliorated by treatment with purpurin, based on changes in cell death, DNA fragmentation, formation of reactive oxygen species, and pro-apoptotic (Bax)/anti-apoptotic (Bcl-2) protein levels. In addition, treatment with purpurin significantly reduced the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK), and p38 signaling in HT22 cells. Transient forebrain ischemia in gerbils led to a significant increase in locomotor activity 1 day after ischemia and significant decrease in number of surviving cells in the CA1 region 4 days after ischemia. Administration of purpurin reduced the travel distance 1 day after ischemia and abrogates the neuronal death in the hippocampal CA1 region 4 days after ischemia based on immunohistochemical and histochemical staining for NeuN and Fluoro-Jade C, respectively. Purpurin treatment significantly decreased the activation of microglia and astrocytes as well as the increases of nuclear factor kappa-light-chain-enhancer of activated B cells p65 in the hippocampal CA1 region 4 days after ischemia and ameliorated the ischemia-induced transient increases of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus 6 h after ischemia. In addition, purpurin significantly alleviated the ischemia-induced phosphorylation of JNK, ERK, and p38 in the hippocampus 1 day after ischemia. Furthermore, purpurin treatment significantly mitigated the increases of Bax in the hippocampus 1 day after ischemia and the lipid peroxidation based on malondialdehyde and hydroperoxides levels 2 days after ischemia. These results suggest that purpurin can be one of the potential candidates to reduce neuronal damage and inflammatory responses after oxidative stress in HT22 cells or ischemic damage in gerbils.

Коррекция куркумином и глицином нарушений легкой степени черепно-мозговой травмы у экспериментальных животных с различной степенью активности

The aim of the research is to study the effect of the phytopreparation curcumin, the synthetic preparationglycine and the curcumin-glycine complex on the organism of animals with mild traumatic brain injury.Material and methods. Preclinical tests of curcumin, glycine and their complex on 90 laboratory whiteoutbred male rats weighing 210 ± 4.8 g, which are kept under standard conditions at the Central ScientificResearch Laboratory of the Tashkent Pharmaceutical Institute. Curcumin, glycine and their administrationat a dose of 75 mg / kg, then, after the reproduction of the model of mild brain injury in animals, the balance (system) was assessed using the «walk on a raised bar» test (walking on a raised bar).Results. The introduction of the curcumin + glycine complex had a more beneficial effect than monotherapy with curcumin and glycine, both on the levels of physical activity and on psychoemotional status.Conclusion. Analysis of the therapeutic effect of curcumin, glycine and curcumin + glycine complex onexperimental models showed that the most effective and rational for the correction of functional disordersin behavior is the use of the curcumin + glycine complex.

A novel time-resolved fluorescent lateral flow immunoassay for quantitative detection of the trauma brain injury biomarker-glial fibrillary acidic protein

A highly sensitive time-resolved fluorescence lateral flow immunoassay (TRF-LFIA) was developed to quantify glial fibrillary acidic protein (GFAP), a trauma brain injury (TBI) biomarker in blood, for the purpose of providing a diagnosis of mild brain injury.

C3a Receptor Signaling Inhibits Neurodegeneration Induced by Neonatal Hypoxic-Ischemic Brain Injury.

Hypoxic-ischemic neonatal encephalopathy due to perinatal asphyxia is the leading cause of brain injury in newborns. Clinical data suggest that brain inflammation induced by perinatal insults can persist for years. We previously showed that signaling through the receptor for complement peptide C3a (C3aR) protects against cognitive impairment induced by experimental perinatal asphyxia. To investigate the long-term neuropathological effects of hypoxic-ischemic injury to the developing brain and the role of C3aR signaling therein, we subjected wildtype mice, C3aR deficient mice, and mice expressing biologically active C3a in the CNS to mild hypoxic-ischemic brain injury on postnatal day 9. We found that such injury triggers neurodegeneration and pronounced reactive gliosis in the ipsilesional hippocampus both of which persist long into adulthood. Transgenic expression of C3a in reactive astrocytes reduced hippocampal neurodegeneration and reactive gliosis. In contrast, neurodegeneration and microglial cell density increased in mice lacking C3aR. Intranasal administration of C3a for 3 days starting 1 h after induction of hypoxia-ischemia reduced neurodegeneration and reactive gliosis in the hippocampus of wildtype mice. We conclude that neonatal hypoxic-ischemic brain injury leads to long-lasting neurodegeneration. This neurodegeneration is substantially reduced by treatment with C3aR agonists, conceivably through modulation of reactive gliosis.

Chronic Administration of 7,8-DHF Lessens the Depression-like Behavior of Juvenile Mild Traumatic Brain Injury Treated Rats at Their Adult Age.

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity among the global youth and commonly results in long-lasting sequelae, including paralysis, epilepsy, and a host of mental disorders such as major depressive disorder. Previous studies were mainly focused on severe TBI as it occurs in adults. This study explored the long-term adverse effect of mild TBI in juvenile animals (mTBI-J). Male Sprague Dawley rats received mTBI-J or sham treatment at six weeks old, then underwent behavioral, biochemical, and histological experiments three weeks later (at nine weeks old). TTC staining, H&E staining, and brain edema measurement were applied to evaluate the mTBI-J induced cerebral damage. The forced swimming test (FST) and sucrose preference test (SPT) were applied for measuring depression-like behavior. The locomotor activity test (LAT) was performed to examine mTBI-J treatment effects on motor function. After the behavioral experiments, the dorsal hippocampus (dHip) and ventral hippocampus (vHip) were dissected out for western blotting to examine the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB). Finally, a TrkB agonist 7,8-DHF was injected intraperitoneally to evaluate its therapeutic effect on the mTBI-J induced behavioral abnormalities at the early adult age. Results showed that a mild brain edema occurred, but no significant neural damage was found in the mTBI-J treated animals. In addition, a significant increase of depression-like behaviors was observed in the mTBI-J treated animals; the FST revealed an increase in immobility, and a decrease in sucrose consumption was found in the mTBI-J treated animals. There were no differences observed in the total distance traveled of the LAT and the fall latency of the rotarod test. The hippocampal BDNF expression, but not the TrkB, were significantly reduced in mTBI-J, and the mTBI-J treatment-induced depression-like behavior was lessened after four weeks of 7,8-DHF administration. Collectively, these results indicate that even a mild juvenile TBI treatment that did not produce motor deficits or significant histological damage could have a long-term adverse effect that could be sustained to adulthood, which raises the depression-like behavior in the adult age. In addition, chronic administration of 7,8-DHF lessens the mTBI-J treatment-induced depression-like behaviors in adult rats. We suggest the potential usage of 7,8-DHF as a therapeutic agent for preventing the long-term adverse effect of mTBI-J.

Association of pulmonary function with mild cognitive impairment and brain pathologies: a community‐based cohort study

AbstractBackgroundThe association of pulmonary function (PF) with mild cognitive impairment (MCI) and its underlying mechanisms remain unclear. We examined the association of PF with MCI and brain pathologies.MethodWithin the Rush Memory and Aging Project, the 1025 no cognitive impairment (NCI) participants (mean age: 79.41±7.77 years) were followed for up to 21 years to detect incident MCI. PF was assessed with a composite score based on forced vital capacity, forced expiratory volume in 1s, and peak expiratory flow measured at baseline, and further divided into tertiles (i.e., lowest, middle, and highest). MCI was diagnosed following standard criteria. During the follow‐up, 396 participants died and underwent autopsies for neuropathological assessment (including Alzheimer’s disease [AD], and vascular brain pathologies). Data were analyzed using Cox regression, Laplace regression, and Logistic regression.ResultDuring the follow‐up (median 7 years, interquartile range 4‐10 years), 461 participants developed MCI. Compared to the highest PF, the multi‐adjusted HR (95% CI) was 2.07 (1.55‐2.78) for MCI. The median time from NCI to MCI development was 4.05 (95% CI: 2.78‐5.31) years shorter in people with the lowest PF than those with the highest PF. In the pathological data analysis, the lowest PF was significantly related to higher AD pathology (odds ratio [OR]: 1.45, 95% CI: 1.29‐1.62) and vascular brain pathologies (OR: 3.47, 95% CI: 1.50‐8.03) compared to the highest PF.ConclusionThe lowest PF is associated with a 2‐fold risk of MCI and accelerates progression from NCI to MCI by more than 4 years. Both neurodegenerative and vascular mechanisms may underlie this association.

Association of blood‐based epigenetic age acceleration with cognitive impairment and brain outcomes by cardiovascular disease among women

AbstractBackgroundDNA methylation‐based epigenetic age acceleration (AgeAccel), an aging biomarker indicating faster biological aging relative to chronological age, is associated with many age‐related phenotypes. Blood‐based AgeAccel has been associated with lower cognitive function in several studies. However, there are limited data on associations of AgeAccel with mild cognitive impairment (MCI), dementia, and brain structure. Further, no prior study investigated whether associations of AgeAccel with cognitive and brain outcomes vary by cardiovascular disease (CVD), despite evidence linking vascular pathologies to both AgeAccel and dementia.MethodParticipants were 615 older women from a case‐cohort study of CVD in the Women’s Health Initiative (WHI) Clinical Trials and Observational Study who also enrolled in the WHI Memory Study (n=327 with incident CVD during follow‐up and n=288 without incident CVD). AgeAccel was measured in blood collected at baseline when women had no CVD or cognitive impairment. Women were followed for up to 25 years to determine centrally adjudicated diagnoses of MCI and dementia according to DSM‐IV criteria. A subset (n=90) had structural brain MRI scans performed ∼8 years after baseline. Associations between four measures of AgeAccel (intrinsic AgeAccel [IEAA], extrinsic AgeAccel [EEAA], AgeAccelPheno, and AgeAccelGrim) and risks for MCI/dementia incidence were estimated using Cox proportional hazards regression models. Associations of AgeAccel with brain volumes were examined using multiple linear regression models. Models were stratified by incident CVD status and adjusted for chronological age and other sociodemographic characteristics, lifestyle behaviors, and clinical factors.ResultAmong women who developed CVD, a 1‐year increase in IEAA was associated with higher risk of MCI (HR=1.10; 95% CI=1.03‐1.18), higher risk of combined MCI/dementia (HR=1.07; 95% CI=1.01‐1.13), and higher ventricular volume (in cm3; β=1.04; 95% CI=0.15‐1.94). A 1‐year increase in AgeAccelPheno was associated with higher risk of combined MCI/dementia (HR=1.05; 95% CI=1.00‐1.10) in women with incident CVD. The other two measures of AgeAccel were not associated with any outcome among women with incident CVD. No associations of AgeAccel with cognitive impairment or brain volumes were observed among women who did not develop CVD.ConclusionBlood‐based AgeAccel may be a marker of cognitive and brain health among women with underlying vascular pathologies.

Journal Digest: Post-COVID Depression; Locus Coeruleus and Alzheimer’s; CY-BOCS Reliability; and More

Journal Digest: Post-COVID Depression; Locus Coeruleus and Alzheimer’s; CY-BOCS Reliability; and More

Self-reported neurobehavioral symptoms in combat veterans: An examination of NSI with mBIAS symptom validity scales and potential effects of psychological distress.

This study evaluated symptom validity scales from the Neurobehavioral Symptom Inventory (NSI) and mild Brain Injury Atypical Symptom Scale (mBIAS) in a sample of 338 combat veterans. Classification statistics were computed using the Structured Inventory of Malingered Symptomatology (SIMS) as the validity criterion. Symptom distress was assessed with the Patient Health Questionnaire-9 and Posttraumatic Stress Disorder (PTSD) Checklist-5. At SIMS > 14, the NSI total score resulted in the highest area under the curve (AUC; .91), followed by Validity-10 (AUC = .88) and mBIAS (AUC = .67). At SIMS > 23, both NSI total and Validity-10 AUCs decreased to .88; in contrast, mBIAS AUC increased to .75. The NSI total score and Validity-10 were interpreted to reflect symptom magnification, whereas the mBIAS may reflect symptom fabrication. There was a subsample with elevated Patient Health Questionnaire-9 (PHQ-9) and PTSD Checklist-5 scores who were significantly distressed but not deemed invalid on the NSI; however, there appears to be an upper threshold on the NSI total score (>69) beyond which nobody produced an invalid score on the SIMS. A recommended approach is provided for using NSI-related validity measures. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Effects of Continuous Nursing on Psychological and Quality of Life of Patients with Mild Brain Trauma

Effects of Continuous Nursing on Psychological and Quality of Life of Patients with Mild Brain Trauma

Microstructural Tissue Changes in a Rat Model of Mild Traumatic Brain Injury.

Our study investigates the potential of diffusion MRI (dMRI), including diffusion tensor imaging (DTI), fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI), to detect microstructural tissue abnormalities in rats after mild traumatic brain injury (mTBI). The brains of sham-operated and mTBI rats 35 days after lateral fluid percussion injury were imaged ex vivo in a 11.7-T scanner. Voxel-based analyses of DTI-, fixel- and NODDI-based metrics detected extensive tissue changes in directly affected brain areas close to the primary injury, and more importantly, also in distal areas connected to primary injury and indirectly affected by the secondary injury mechanisms. Histology revealed ongoing axonal abnormalities and inflammation, 35 days after the injury, in the brain areas highlighted in the group analyses. Fractional anisotropy (FA), fiber density (FD) and fiber density and fiber bundle cross-section (FDC) showed similar pattern of significant areas throughout the brain; however, FA showed more significant voxels in gray matter areas, while FD and FDC in white matter areas, and orientation dispersion index (ODI) in areas most damage based on histology. Region-of-interest (ROI)-based analyses on dMRI maps and histology in selected brain regions revealed that the changes in MRI parameters could be attributed to both alterations in myelinated fiber bundles and increased cellularity. This study demonstrates that the combination of dMRI methods can provide a more complete insight into the microstructural alterations in white and gray matter after mTBI, which may aid diagnosis and prognosis following a mild brain injury.

Клініко-неврологічні особливості перебігу та вміст нейроамінокислот у хворих із віддаленими наслідками легкої закритої черепно-мозкової травми

Нами обстежено 38 пацієнтів (11 жінок (28,94 %) та 27 чоловіків (71,06 %)) із віддаленими наслідками легкої закритої черепно-мозкової травми; вік хворих становив від 26 до 58 років (середній вік 43,61 ± 8,24 року). Уміст нейроамінокислот (глутамат, аспартат, ГАМК) у сироватці крові вимірювали спектрофотометричним методом для вивчення їх патогенетичного впливу на формування віддалених наслідків легкої закритої черепно-мозкової травми. Показано, що в пацієнтів із віддаленими наслідками легкої закритої черепно-мозкової травми, які зазнали забій головного мозку легкого ступеня тяжкості (39,48 %), відзначаються найбільш виражені зміни вмісту нейроамінокислот, що проявляються в збільшенні рівня глутамату (246,25 ± 21,39 мкмоль/л порівняно з контрольною групою — 112,75 ± 11,72 мкмоль/л) та зменшенні рівня ГАМК (2,10 ± 1,16 мкмоль/л порівняно з контрольною групою — 6,72 ± 1,59 мкмоль/л). Формування віддалених наслідків легкої закритої черепно-мозкової травми супроводжувалося розладами вегетативної регуляції, що проявлялося в парасимпатичній направленості вегетативного тонусу, виявленій в більшості пацієнтів 1-ї групи (78,26 %) та у 86,67 % пацієнтів 2-ї групи, що може також відігравати значну роль у патогенезі захворювання й формуванні віддалених наслідків легкої закритої черепно-мозкової травми, має важливе клініко-прогностичне значення в подальшому розвитку травматичної енцефалопатії, що треба враховувати при подальшому лікуванні.

N-3 Polyunsaturated Fatty Acids Ameliorate Neurobehavioral Outcomes Post-Mild Traumatic Brain Injury in the Fat-1 Mouse Model.

Concussions and mild traumatic brain injury (m-TBI) have been identified as a consequential public health concern because of their potential to cause considerable impairments in physical, cognitive, behavioral, and social functions. Given their prominent structural and functional roles in the brain, n-3 polyunsaturated fatty acids (PUFA) have been identified as a potentially viable prophylactic agent that may ameliorate the deleterious effects of m-TBI on brain function. The purpose of the present pilot study was to investigate the effect of n-3 PUFA on neurologic function using a weight drop injury (WDI) model. Fat-1 mice, capable of synthesizing n-3 PUFA endogenously from n-6 PUFA, and their wild-type (WT) counterparts, were subjected to a mild low-impact WDI on the closed cranium, and recovery was evaluated using the neurological severity score (NSS) to assess the motor and neurobehavioral outcomes. In comparison to the WT mice, the fat-1 mice had a significantly (p ≤ 0.05) lower NSS at all time points post-WDI, and significantly greater neurological restoration measured as the time to first movement. Overall, these findings demonstrate the protective effect of n-3 PUFA against mild brain injury.

Prediction of posttraumatic stress disorder by acute stress disorder in traffic accident survivors.

To investigate the predictive effect of different symptoms of early acute stress disorder (ASD) on posttraumatic stress disorder (PTSD) in traffic accident survivors. A total of 206 traffic accident survivors were assessed with the acute stress disorder scale (ASDS) within 2-23 days after accidents, as well as with 17-item PTSD checklist-specific stressor version (PCL-S) during 4-12 months after accidents. All into the first group of subjects by senior surgeon assessment, based on the clinical, radiological and laboratory examination, excluded traumatic brain injuries, and mild brain injury. And then, assessment by clinical psychological practitioner. The severity of ASD can significantly predict the severity of PTSD symptoms. ASD reexperience symptoms and avoidance symptoms can significantly predict PTSD reexperience symptoms and avoidance symptoms. ASD hyperarousal symptoms can significantly predict PTSD hyperarousal symptoms. ASD and PTSD are common psychological disorders among traffic accident survivors. ASD can predict the symptoms and severity of PTSD.

Analysis of Neuron Specific Enolase Serum Levels in Traumatic Brain Injury

Background : Traumatic brain injury is still the main cause of death and disability in productive age. Assessment the level of consciousness and imaging examinations after a brain injury can not always describe the severity of damage in the brain, this is because the pathological process is still ongoing due to secondary brain injury. Therefore, it is necessary to examine biomarkers that can describe the severity of the pathological process that occurs. The purpose of this study was to assess serum neuron-specific enolase (NSE) levels and their relationship to the severity and outcome of a traumatic brain injury.
 Methods : A cross sectional design was conducted in the emergency department of DR M Djamil Hospital, Padang. There were 72 patients who met the inclusion criteria. A Glasgow Coma Scale examination was performed to assess the severity of brain injury and examination of NSE serum levels at 48 hours post- injury using ELISA technique and assess the Glasgow outcome scale (GOS) at 6 weeks post-injury. Data analysis using SPSS 22 program, the results are significance if the p value <0.05 
 Results : The average NSE level was higher in severe brain injuries than moderate and mild brain injuries and this difference was statistically significant (p<0.05). The NSE serum levels were higher in poor outcomes than in good outcomes and this difference was statistically significant (p<0.05). 
 Conclusion : High NSE serum levels in the acute phase were associated with the severity of the brain injury and poor outcome 6 weeks after the brain injury.

The Effect of Mild Traumatic Brain Injury on Cerebral Microbleeds in Aging.

A traumatic brain injury (TBI) induces the formation of cerebral microbleeds (CMBs), which are associated with cognitive impairments, psychiatric disorders, and gait dysfunctions in patients. Elderly people frequently suffer TBIs, especially mild brain trauma (mTBI). Interestingly, aging is also an independent risk factor for the development of CMBs. However, how TBI and aging may interact to promote the development of CMBs is not well established. In order to test the hypothesis that an mTBI exacerbates the development of CMBs in the elderly, we compared the number and cerebral distribution of CMBs and assessed them by analysing susceptibility weighted (SW) MRI in young (25 ± 10 years old, n = 18) and elder (72 ± 7 years old, n = 17) patients after an mTBI and in age-matched healthy subjects (young: 25 ± 6 years old, n = 20; aged: 68 ± 5 years old, n = 23). We found significantly more CMBs in elder patients after an mTBI compared with young patients; however, we did not observe a significant difference in the number of cerebral microhemorrhages between aged and aged patients with mTBI. The majority of CMBs were found supratentorially (lobar and basal ganglion). The lobar distribution of supratentorial CMBs showed that aging enhances the formation of parietal and occipital CMBs after mTBIs. This suggests that aging and mTBIs do not synergize in the induction of the development of CMBs, and that the different distribution of mTBI-induced CMBs in aged patients may lead to specific age-related clinical characteristics of mTBIs.

Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury.

Although traumatic brain injury (TBI) acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of mild TBI (mTBI), we found a chronic increase in C1q expression specifically in the corticothalamic system. Increased C1q expression colocalized with neuron loss and chronic inflammation and correlated with disruption in sleep spindles and emergence of epileptic activities. Blocking C1q counteracted these outcomes, suggesting that C1q is a disease modifier in mTBI. Single-nucleus RNA sequencing demonstrated that microglia are a source of thalamic C1q. The corticothalamic circuit could thus be a new target for treating TBI-related disabilities.