OBJECTIVES: To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI). METHODS: A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge. RESULTS: Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF-α, and IL-1β on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1β on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1β than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05). CONCLUSIONS Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI.
Child ; Humans ; Valproic Acid/therapeutic use* ; HMGB1 Protein ; Pilot Projects ; Tumor Necrosis Factor-alpha ; Neuroinflammatory Diseases ; NLR Family, Pyrin Domain-Containing 3 Protein ; Prospective Studies ; Brain Injuries, Traumatic/pathology*

OBJECTIVES: To investigate the characteristics and objective assessment method of visual field defects caused by optic chiasm and its posterior visual pathway injury. METHODS: Typical cases of visual field defects caused by injuries to the optic chiasm, optic tracts, optic radiations, and visual cortex were selected. Visual field examinations, visual evoked potential (VEP) and multifocal visual evolved potential (mfVEP) measurements, craniocerebral CT/MRI, and retinal optical coherence tomography (OCT) were performed, respectively, and the aforementioned visual electrophysiological and neuroimaging indicators were analyzed comprehensively. RESULTS: The electrophysiological manifestations of visual field defects caused by optic chiasm injuries were bitemporal hemianopsia mfVEP abnormalities. The visual field defects caused by optic tract, optic radiation, and visual cortex injuries were all manifested homonymous hemianopsia mfVEP abnormalities contralateral to the lesion. Mild relative afferent pupil disorder (RAPD) and characteristic optic nerve atrophy were observed in hemianopsia patients with optic tract injuries, but not in patients with optic radiation or visual cortex injuries. Neuroimaging could provide morphological evidence of damages to the optic chiasm and its posterior visual pathway. CONCLUSIONS Visual field defects caused by optic chiasm, optic tract, optic radiation, and visual cortex injuries have their respective characteristics. The combined application of mfVEP and static visual field measurements, in combination with neuroimaging, can maximize the assessment of the location and degree of visual pathway damage, providing an effective scheme for the identification of such injuries.
Humans ; Optic Chiasm/pathology* ; Visual Pathways/pathology* ; Visual Fields ; Evoked Potentials, Visual ; Random Amplified Polymorphic DNA Technique ; Hemianopsia/complications* ; Vision Disorders/pathology* ; Optic Nerve Injuries/diagnostic imaging* ; Brain Injuries, Traumatic/diagnostic imaging*

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.
Animals ; Brain Injuries, Traumatic/pathology* ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology* ; Recovery of Function ; Tumor Necrosis Factor Inhibitors

OBJECTIVE: To determine whether Schisandrin B (Sch B) attenuates early brain injury (EBI) in rats with subarachnoid hemorrhage (SAH). METHODS: Sprague-Dawley rats were divided into sham (sham operation), SAH, SAH+vehicle, and SAH+Sch B groups using a random number table. Rats underwent SAH by endovascular perforation and received Sch B (100 mg/kg) or normal saline after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evan's blue extravasation, and terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining were carried out 24 h after SAH. Immunofluorescent staining was performed to detect the expressions of ionized calcium binding adapter molecule 1 (Iba-1) and myeloperoxidase (MPO) in the rat brain, while the expressions of B-cell lymphoma 2 (Bcl-2), Bax, Caspase-3, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated specklike protein containing the caspase-1 activator domain (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in the rat brains were detected by Western blot. RESULTS: Compared with the SAH group, Sch B significantly improved the neurological function, reduced brain water content, Evan's blue content, and apoptotic cells number in the brain of rats (P<0.05 or P<0.01). Moreover, Sch B decreased SAH-induced expressions of Iba-1 and MPO (P<0.01). SAH caused the elevated expressions of Bax, Caspase-3, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in the rat brain (P<0.01), all of which were inhibited by Sch B (P<0.01). In addition, Sch B increased the Bcl-2 expression (P<0.01). CONCLUSION Sch B attenuated SAH-induced EBI, which might be associated with the inhibition of neuroinflammation, neuronal apoptosis, and the NLRP3 inflammatory signaling pathway.
Animals ; Apoptosis ; Brain/pathology* ; Brain Injuries/pathology* ; Caspase 3/metabolism* ; Cyclooctanes ; Evans Blue ; Inflammasomes/metabolism* ; Interleukin-18/metabolism* ; Lignans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Polycyclic Compounds ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage/drug therapy* ; Water ; bcl-2-Associated X Protein/metabolism*

Neuroinflammation is a key contributor to the pathogenic cascades induced by hypoxic-ischemic (HI) insult in the neonatal brain. AD-16 is a novel anti-inflammatory compound, recently found to exert potent inhibition of the lipopolysaccharide-induced production of pro-inflammatory and neurotoxic mediators. In this study, we evaluated the effect of AD-16 on primary astrocytes and neurons under oxygen-glucose deprivation (OGD) in vitro and in mice with neonatal HI brain injury in vivo. We demonstrated that AD-16 protected against OGD-induced astrocytic and neuronal cell injury. Single dose post-treatment with AD-16 (1 mg/kg) improved the neurobehavioral outcome and reduced the infarct volume with a therapeutic window of up to 6 h. Chronic administration reduced the mortality rate and preserved whole-brain morphology following neonatal HI. The in vitro and in vivo effects suggest that AD-16 offers promising therapeutic efficacy in attenuating the progression of HI brain injury and protecting against the associated mortality and morbidity.
Animals ; Animals, Newborn ; Astrocytes/pathology* ; Brain/pathology* ; Brain Injuries/pathology* ; Glucose ; Hypoxia ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Neuroinflammatory Diseases ; Neuroprotective Agents/therapeutic use* ; Oxygen/therapeutic use*

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b⁺ pericytes after TBI. These CD11b⁺ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b^- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
Blood-Brain Barrier/metabolism* ; Brain/pathology* ; Brain Injuries, Traumatic/metabolism* ; Extracellular Traps/metabolism* ; Histones ; Humans ; Lectins, C-Type ; Pericytes/pathology*

We present the case of a 23-year-old man who suddenly collapsed during a physical altercation with his friends while in a drunken state. The post-mortem computed tomography (CT) with angiography revealed acute basal subarachnoid hemorrhage with rupture of the left middle cerebral artery. On autopsy, the head, face, mandible and neck showed multifocal hemorrhages with fracture of the hyoid bone, and the pathologic findings of the brain was consistent with CT findings. However, the vascular rupture site was not observed macroscopically. On histologic examination, a microscopic focal rupture was identified at the proximal portion of the middle cerebral artery, and possibility of arteriopathy was considered. This case illustrates that other parts of intracerebral arteries (other than the vertebral arteries) can be the culprit of rupture in the case of traumatic basal subarachnoid hemorrhage, and the post-mortem angiographic findings can be helpful in targeting the site of vascular injury. Furthermore, meticulous sampling of intracranial vessels could help find the vascular rupture site and identify any histologic findings suspicious of arteriopathy. Therefore, we suggest that post-mortem angiography can be an effective and adjunctive tool for a tailored approach in finding the vascular injury, and that histologic examination of both the intracranial and extracranial arteries be important to medicolegally ensure the death of traumatic basal subarachnoid hemorrhage and to examine presence of arteriopathy as a predisposing factor.
Angiography ; Arteries ; Autopsy ; Brain ; Causality ; Forensic Pathology ; Friends ; Head ; Hemorrhage ; Humans ; Hyoid Bone ; Mandible ; Middle Cerebral Artery ; Neck ; Rupture ; Subarachnoid Hemorrhage ; Subarachnoid Hemorrhage, Traumatic ; Vascular System Injuries ; Young Adult

OBJECTIVES: To study the forensic features of diffuse brain atrophy after trauma, the relationship between age and interval time of post-traumatic brain atrophy, and the relationship between the degree of craniocerebral injury and that of brain atrophy. METHODS: The forensic features of 25 cases of diffuse brain atrophy after craniocerebral trauma were retrospectively analyzed from aspects of gender, age, craniocerebral injury characteristics, and imaging characteristics of brain atrophy. Pearson correlation analysis was used for statistical analysis. RESULTS: Diffuse brain atrophy after trauma could occur in any age group, dominated by severe brain injury. The Pearson correlation coefficients （r） between the time interval of brain atrophy and age were 0.442 （ P<0.05）, 0.341 （P>0.05）, and 0.904 （ P<0.05） for the overall cases, the group over age 50, and the group under age 50, respectively. The correlation coefficient between the degree of brain injury and that of brain atrophy was 0.579 （ P<0.05）, and that between severe brain injury and brain atrophy was 0.788 （ P<0.05）. CONCLUSIONS The more serious the brain injury, the more severe the brain atrophy. Various degrees of diffuse brain atrophy can occur in severe craniocerebral injury, and diffuse brain atrophy is usually mild and moderate after mild and moderate craniocerebral injury. In the practice of forensic clinical identification, a comprehensive analysis should be conducted with the combination of case materials when the identified person has high risk factors leading to brain atrophy （e.g., hypertension, diabetes, etc.）, plus injury and illness relationship analysis if necessary.
Atrophy ; Brain/pathology* ; Brain Injuries/complications* ; Craniocerebral Trauma ; Humans ; Retrospective Studies

Objective To investigate the expression of cannabinoid type 2 receptor （CB2R） at different time points after brain contusion and its relationship with wound age of mice. Methods A mouse brain contusion model was established with PCI3000 Precision Cortical Impactor. Expression changes of CB2R around the injured area were detected with immunohistochemical staining, immunofluorescent staining and Western blotting at different time points. Results Immunohistochemical staining results showed that only a few cells in the cerebral cortex of the sham operated group had CB2R positive expression. The ratio of CB2R positive cells gradually increased after injury and reached the peak twice at 12 h and 7 d post-injury, followed by a decrease to the normal level 28 d post-injury. The results of Western blotting were consistent with the immunohistochemical staining results. Immunofluorescent staining demonstrated that the changes of the ratio of CB2R positive cells in neurons, CB2R positive cells in monocytes and CB2R positive cells in astrocytes to the total cell number showed a single peak pattern, which peaked at 12 h, 1 d and 7 d post-injury, respectively. Conclusion The expression of CB2R after brain contusion in neurons, monocytes and astrocytes in mice suggests that it is likely to be involved in the regulation of the biological functions of those cells. The changes in CB2R are time-dependent, which suggests its potential applicability as a biological indicator for wound age estimation of brain contusion in forensic practice.
Animals ; Blotting, Western ; Brain Contusion/metabolism* ; Brain Injuries ; Forensic Pathology ; Mice ; Muscle, Skeletal/pathology* ; Receptor, Cannabinoid, CB2/metabolism* ; Receptors, Cannabinoid ; Time Factors ; Wound Healing/physiology*

PURPOSETo investigate the effects of estrogen G protein-coupled receptor 30 (GPR30) agonist G1 on hippocampal neuronal apoptosis and microglial polarization in rat traumatic brain injury (TBI).

METHODSMale SD rats were randomly divided into sham group, TBI + vehicle group, TBI + G1 group. Experimental moderate TBI was induced using Feeney's weigh-drop method. G1 (100μg/kg) or vehicle was intravenously injected from femoral vein at 30 min post-injury. Rats were sacrificed at 24 h after injury for detection of neuronal apoptosis and microglia polarization. Neuronal apoptosis was assayed by immunofluorescent staining of active caspase-3. M1 type microglia markers (iNOS and IL-1β) and M2 type markers (Arg1 and IL-4) were examined by immunoblotting or ELISA. Total protein level of Akt and phosphorylated Akt were assayed by immunoblotting.

RESULTSG1 significantly reduced active caspase-3 positive neurons in hippocampus. Meanwhile G1 increased the ratio of Arg1/iNOS. IL-1β production was decreased but IL-4 was increased after G1 treatment. G1 treatment also increased the active form of Akt.

CONCLUSIONSGPR30 agonist G1 inhibited neuronal apoptosis and favored microglia polarization to M2 type.

Animals ; Apoptosis ; drug effects ; Brain Injuries, Traumatic ; drug therapy ; pathology ; Cell Polarity ; Hippocampus ; drug effects ; Interleukin-1beta ; biosynthesis ; Male ; Microglia ; drug effects ; Neurons ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; agonists