Systemic Elevation of n-3 Polyunsaturated Fatty Acids (n-3-PUFA) Is Associated with Protection against Visual, Motor, and Emotional Deficits in Mice following Closed-Head Mild Traumatic Brain Injury.

Traumatic brain injury (TBI) causes neuroinflammation and neurodegeneration leading to various pathological complications such as motor and sensory (visual) deficits, cognitive impairment, and depression. N-3 polyunsaturated fatty acid (n-3 PUFA) containing lipids are known to be anti-inflammatory, whereas the sphingolipid, ceramide (Cer), is an inducer of neuroinflammation and degeneration. Using Fat1+-transgenic mice that contain elevated levels of systemic n-3 PUFA, we tested whether they are resistant to mild TBI-mediated sensory-motor and emotional deficits by subjecting Fat1-transgenic mice and their WT littermates to focal cranial air blast (50 psi) or sham blast (0 psi, control). We observed that visual function in WT mice was reduced significantly following TBI but not in Fat1+-blast animals. We also found Fat1+-blast mice were resistant to the decline in motor functions, depression, and fear-producing effects of blast, as well as the reduction in the area of oculomotor nucleus and increase in activated microglia in the optic tract in brain sections seen following blast in WT mice. Lipid and gene expression analyses confirmed an elevated level of the n-3 PUFA eicosapentaenoic acid (EPA) in the plasma and brain, blocking of TBI-mediated increase of Cer in the brain, and decrease in TBI-mediated induction of Cer biosynthetic and inflammatory gene expression in the brain of the Fat1+ mice. Our results demonstrate that suppression of ceramide biosynthesis and inflammatory factors in Fat1+-transgenic mice is associated with significant protection against the visual, motor, and emotional deficits caused by mild TBI. This study suggests that n-3 PUFA (especially, EPA) has a promising therapeutic role in preventing neurodegeneration after TBI.

Association of Cavum Septum Pellucidum and Cavum Vergae With Cognition, Mood, and Brain Volumes in Professional Fighters.

Importance: Many studies have investigated the imaging findings showing sequelae of repetitive head trauma, with mixed results. Objective: To determine whether fighters (boxers and mixed martial arts fighters) with cavum septum pellucidum (CSP) and cavum vergae (CV) have reduced volumes in various brain structures or worse clinical outcomes on cognitive and mood testing. Design, Setting, and Participants: This cohort study assessed participants from the Professional Fighters Brain Health Study. Data were collected from April 14, 2011, to January 17, 2018, and were analyzed from September 1, 2018, to May 23, 2019. This study involved a referred sample of 476 active and retired professional fighters. Eligible participants were at least 18 years of age and had at least a fourth-grade reading level. Healthy age-matched controls with no history of trauma were also enrolled. Exposures: Presence of CSP, CV, and their total (additive) length (CSPV length). Main Outcomes and Measures: Information regarding depression, impulsivity, and sleepiness among study participants was obtained using the Patient Health Questionnaire depression scale, Barrett Impulsiveness Scale, and the Epworth Sleepiness Scale. Cognition was assessed using raw scores from CNS Vital Signs. Volumes of various brain structures were measured via magnetic resonance imaging. Results: A total of 476 fighters (440 men, 36 women; mean [SD] age, 30.0 [8.2] years [range, 18-72 years]) and 63 control participants (57 men, 6 women; mean [SD] age, 30.8 [9.6] years [range, 18-58 years]) were enrolled in the study. Compared with fighters without CV, fighters with CV had significantly lower mean psychomotor speed (estimated difference, -11.3; 95% CI, -17.4 to -5.2; P = .004) and lower mean volumes in the supratentorium (estimated difference, -31 191 mm3; 95% CI, -61 903 to -479 mm3; P = .05) and other structures. Longer CSPV length was associated with lower processing speed (slope, -0.39; 95% CI, -0.49 to -0.28; P < .001), psychomotor speed (slope, -0.43; 95% CI, -0.53 to -0.32; P < .001), and lower brain volumes in the supratentorium (slope, -1072 mm3 for every 1-mm increase in CSPV length; 95% CI, -1655 to -489 mm3; P < .001) and other structures. Conclusions and Relevance: This study suggests that the presence of CSP and CV is associated with lower regional brain volumes and cognitive performance in a cohort exposed to repetitive head trauma.

Differential effects of minocycline on microglial activation and neurodegeneration following closed head injury in the neonate rat.

The role of microglia in the pathophysiology of injury to the developing brain has been extensively studied. In children under the age of 4 who have sustained a traumatic brain injury (TBI), markers of microglial/macrophage activation were increased in the cerebrospinal fluid and were associated with worse neurologic outcome. Minocycline is an antibiotic that decreases microglial/macrophage activation following hypoxic-ischemia in neonatal rodents and TBI in adult rodents thereby reducing neurodegeneration and behavioral deficits. In study 1, 11-day-old rats received an impact to the intact skull and were treated for 3days with minocycline. Immediately following termination of minocycline administration, microglial reactivity was reduced in the cortex and hippocampus (p<0.001) and was accompanied by an increase in the number of fluoro-Jade B profiles (p<0.001) suggestive of a reduced clearance of degenerating cells; however, this effect was not sustained at 7days post-injury. Although microglial reactivity was reduced in the white matter tracts (p<0.001), minocycline treatment did not reduce axonal injury or degeneration. In the thalamus, minocycline treatment did not affect microglial reactivity, axonal injury and degeneration, and neurodegeneration. Injury-induced spatial learning and memory deficits were also not affected by minocycline. In study 2, to test whether extended dosing of minocycline may be necessary to reduce the ongoing pathologic alterations, a separate group of animals received minocycline for 9days. Immediately following termination of treatment, microglial reactivity and neurodegeneration in all regions examined were exacerbated in minocycline-treated brain-injured animals compared to brain-injured animals that received vehicle (p<0.001), an effect that was only sustained in the cortex and hippocampus up to 15days post-injury (p<0.001). Whereas injury-induced spatial learning deficits remained unaffected by minocycline treatment, memory deficits appeared to be significantly worse (p<0.05). Sex had minimal effects on either injury-induced alterations or the efficacy of minocycline treatment. Collectively, these data demonstrate the differential effects of minocycline in the immature brain following impact trauma and suggest that minocycline may not be an effective therapeutic strategy for TBI in the immature brain.

[Medical care to patients with remote consequences of traumatic craniocerebral injury using methods of reflexology].

Head injury--is an important medical and social problem. In recent years Ukraine prevalence rate of patients with TBI is growing and now is 4-4,2 cases per 100 thousand population. In 50-80% or 2 of the 3 victims formed long-term consequences of closed head injuries that occur with frequent decompensation states with a temporary disability, often (11-12% of patients) have a strong disability. Use in osnovnovnomu acupuncture points of general application, segmental acupuncture points in the head, neck and scalp area. Treatment ought to be lengthy, with mnohorazovym conducting repeated courses. Most often, the following AND: VB(XI)20, VB(XI)21, T(XII)14, T(XII)20, GI(II)11, GI(II)15, GI(II)10, IG(VI)3, IG(VI)15, IG(VI)16, TR(X)5, TR(X)9, C(V)5, MC(IX)5, MC(IX)6, V(VII)40, V(VII)62, VB(XI)34, VB(XI)30, E(III)36, RP(IV)6. Take Effect braking method.

[Severe head injuries during Judo practice].

The goal of this study is to elucidate the characteristic features of Judo head injuries and to propose safety measures and a reaction manual on how to prevent and to deal with such accidents in Japan. Thirty cases of severe head injuries suffered during Judo practice were enrolled in this study. They have made insurance claims for damage compensation and inquiries about Judo accidents attributed to the All Japan Judo Federation, from 2003 to 2010. The average age of the patients was 16.5 year old. The incidence of injury showed 2 peaks in different academic grade levels; one is in the first year of junior high-school (30.0%, n=9) and the other is in senior high school (26.7%, n=8). Around half of them were beginners. Four cases (13.3%) had past history of head trauma or headache and dizziness before a catastrophic accident, suggesting the presence of a second impact. Lucid interval was observed in 25 cases (83.3%). Most patients (93.3%) suffered acute subdural hematoma associated with avulsion of a cerebral bridging vein. Of patients who underwent emergency removal of the hematoma, 15 patients (50%) died and 7 patients (23.3%) entered a persistent vegetative state. Based on these findings, we propose an emergency manual with safety measures for effectively preventing and treating Judo head injuries in an appropriate manner. To reduce the disastrous head injuries in Judo, the safety measures and an optimal action manual should be reconsidered and widely spread and accepted by society.

ECoG studies of valproate, carbamazepine and halothane in frontal-lobe epilepsy induced by head injury in the rat.

The use of electrocorticography (ECoG) with etiologically realistic epilepsy models promises to facilitate the discovery of better anti-epileptic drugs (AEDs). However, this novel approach is labor intensive, and must be optimized. To this end, we employed rostral parasagittal fluid percussion injury (rpFPI) in the adolescent rat, which closely replicates human contusive closed head injury and results in posttraumatic epilepsy (PTE). We systematically examined variables affecting the power to detect anti-epileptic effects by ECoG and used a non-parametric bootstrap strategy to test several different statistics, study designs, statistical tests, and impact of non-responders. We found that logarithmically transformed data acquired in repeated-measures experiments provided the greatest statistical power to detect decreases in seizure frequencies of preclinical interest with just 8 subjects and with up to approximately 40% non-responders. We then used this optimized design to study the anti-epileptic effects of acute exposure to halothane, and chronic (1 week) exposures to carbamazepine (CBZ) and valproate (VPA) 1 month post-injury. While CBZ was ineffective in all animals, VPA induced, during treatment, a progressive decrease in seizure frequency in animals primarily suffering from non-spreading neocortical seizures, but was ineffective in animals with a high frequency of spreading seizures. Halothane powerfully blocked all seizure activity. The data show that rpFPI and chronic ECoG can conveniently be employed for the evaluation of AEDs, suggest that VPA may be more effective than CBZ to treat some forms of PTE, and support the theory that pharmacoresistance may depend on the severity of epilepsy. The data also demonstrate the utility of chronic exposures to experimental drugs in preclinical studies and highlight the need for greater attention to etiology in clinical studies of AEDs.

Factors affecting the development of hypothalamus and pituitary lesions in fatal closed head injury: a prospective study.

OBJECTIVES: To determine the factors affecting the development of pituitary and hypothalamic lesions after fatal closed head injury. MATERIALS: Thirty-four patients with severe closed head injury succumbing to the effects of brain trauma before or during admission, whether managed conservatively or surgically, formed the study group. Clinical parameters, injury to death interval, radiologic data, and management details were taken into consideration. Autopsy was performed within 48 hours of death; hypothalamus and pituitary were carefully removed and evaluated for the presence of lesions on hematoxylin and eosin and immunohistochemical staining. RESULTS: Patients were categorized into early death group (n = 11, those succumbing before/on admission) and late death group (n = 23, those succumbing after admission). Histopathologic evaluation of pituitary revealed capsular hemorrhages in 50%, posterior pituitary hemorrhage in 25%, anterior pituitary infarct in 21.8%, and anterior pituitary hemorrhage in 6.2% patients. Hypothalamic hemorrhage was observed in 65.2% patients and infarcts in 17.3%. Lesions in hypothalamus and pituitary were significantly related to the presence of ventricular compression on computed tomography scan and survival of >24 hours after injury (p < 0.05). Capsular hemorrhage, anterior pituitary hemorrhage, and posterior pituitary hemorrhage were present in 40%, 10%, and 30% of the patients in the early death group when compared with 54.5%, 4.5%, and 22.7% of the patients in the late death group. Anterior pituitary infarcts were present in 10% of the patients with early deaths and 27.3% patients in the late death group. Hypothalamic hemorrhages were present in 44.4% of patients in early death and 78.6% in late death groups. Hypothalamic infarcts (40%) were present in the late death group only. Two patients (25%) in the early death group and 11 (84.6%) in the late death group had lesions in pituitary as well as hypothalamus (p < 0.05). CONCLUSIONS: Presence of ventricular compression on computed tomography scan and survival >24 hours after severe head injury has a significant correlation with the development of hypothalamic and pituitary lesions. Secondary insults account for a proportion of pituitary and hypothalamic lesions after trauma, which may be amenable to prevention by early intervention to treat raised intracranial pressure (ICP)/herniation.

Entrainment of stage 2 sleep spindles by weak, transcerebral magnetic stimulation in an "epileptic" woman.

The proportions of Stage 2 spindles present per second over the prefrontal and temporal lobes of a patient who had been experiencing complex partial epileptic-like experiences and disturbances in sleep patterns for four years following a closed head injury were measured while a weak (1 microT) burst-firing magnetic field was applied transcerebrally through the temporoparietal regions. In several successive segments during the exposure the onsets of the spindles were significantly correlated (rhos between 0.30 and 0.40) with the onset of the field that was presented once every 3 s for about 0.7 s. Lag/lead analyses indicated only the contemporary occurrence of the fields and the spindles were significantly correlated over time. These results suggest that some states of consciousness, particularly those associated with the "epilepsy spectrum disorder" may be more sensitive to entrainment or "synchronization" by weak complex magnetic fields whose temporal structures are designed to simulate natural brain activity.

Organized intrasylvian subarachnoid hematoma in post-traumatic child with dyskinesia for 8 years: a case report and review of the literature.

OBJECT: The authors present their experience with an organized intrasylvian subarachnoid hematoma (OISH) in a post-traumatic pediatric patient with dyskinesia for nearly 8 years. METHODS: An 11-year-old Chinese boy was admitted to the authors' hospital because of dyskinesia in his right upper and lower extremities. When he was 18 months old, he fell down from a trolley and then his mouth drooped to a right angle. The brain computer tomography (CT) revealed a space-occupying lesion in his left temporoparietal region. The symptom improved after 20 days of acupuncture therapy in local hospital. Two years later when he was 4 years old, his right lower limb became lame gradually with sensorial deficit. A concealed arteriovenous malformation was suggested by the brain magnetic resonance imaging and magnetic resonance angiography at that time. The child had been treated with ginkgo biloba leaf extract from 2001 to 2007 and the symptom improved gradually during that period. However, the symptom of his right upper and lower extremities deteriorated continually since January 2007. He fell down again when he was walking 1 month before he was admitted to the authors' department in July 2007. An enlarged left pterional craniotomy was performed to remove the lesion. Histopathology diagnosis was compatible with an organized hematoma with remote hemorrhage and gliosis. The child is presently healthy after 1 year's follow-up. CONCLUSION: The rarity of an OISH in a post-traumatic pediatric patient with dyskinesia for nearly 8 years makes this case very peculiar. This is the first reported pediatric case of OISH found in the literature.

Dystonia associated with pontomesencephalic lesions.

Secondary dystonia is well known subsequent to lesions of the basal ganglia or the thalamus. There is evidence that brainstem lesions may also be associated with dystonia, but little is known about pathoanatomical correlations. Here, we report on a series of four patients with acquired dystonia following brainstem lesions. There were no basal ganglia or thalamic lesions. Three patients suffered tegmental pontomesencephalic hemorrhage and one patient diffuse axonal injury secondary to severe craniocerebral trauma. Dystonia developed with a delay of 1 to 14 months, at a mean delay of 6 months. The patients' mean age at onset was 33 years (range 4-56 years). All patients presented with hemidystonia combined with cervical dystonia, and two patients had craniofacial dystonia in addition. Three patients had postural or kinetic tremors. Dystonia was persistent in three patients, and improved gradually in one. There was little response to medical treatment. One patient with hemidystonia combined with cervical dystonia improved after thalamotomy. Overall, the phenomenology of secondary dystonia due to pontomesencephalic lesions is similar to that caused by basal ganglia or thalamic lesions. Structures involved include the pontomesencephalic tegmentum and the superior cerebellar peduncles. Such lesions are often associated with fatal outcome. While delayed occurrence of severe brainstem dystonia appears to be rare, it is possible that mild manifestations of dystonia might be ignored or not be emphasized in the presence of other disabling deficits.

[Cerebellar infarction in a young adult due to traumatic vertebral artery dissection after lateral mass fracture at the sixth cervical vertebrae].

A 23-years-old man fell off stairs and got a blow on the left head and right shoulder. He felt dysesthesia at the right thumb on the following day, and received chiropractic therapy from the forth day after injury. On the sixth day after injury, he developed dizziness and nausea, and was urgently hospitalized in our cerebrovascular center. On admission, he had horizontal nystagmus and truncal ataxia. Diffusion-weighted magnetic resonance imaging showed high intensity lesions in right cerebellum hemisphere of posterior inferior cerebellar artery territory, indicating fresh infarcts. On angiogram, right vertebral artery showed tapering occlusion at C6 level, indicating dissection. Computed tomogram showed fracture of the right lateral mass at C6 which extended into the transverse foramen. Under diagnosis of the traumatic vertebral artery dissection due to cervical fracture, we started anticoagulation therapy, which was followed by oral antiplatelet therapy in the chronic stage. Extracranial vertebral artery dissection due to cervical fracture is an important cause of brain infarction in a young adult. Radiological examinations are necessary to rule out traumatic vertebral artery dissection for patients with prolonged dizziness after head injury.

Structure and function in acquired prosopagnosia: lessons from a series of 10 patients with brain damage.

Acquired prosopagnosia varies in both behavioural manifestations and the location and extent of underlying lesions. We studied 10 patients with adult-onset lesions on a battery of face-processing tests. Using signal detection methods, we found that discriminative power for the familiarity of famous faces was most reduced by bilateral occipitotemporal lesions that involved the fusiform gyri, and better preserved with unilateral right-sided lesions. Tests of perception of facial structural configuration showed severe deficits with lesions that included the right fusiform gyrus, whether unilateral or bilateral. This deficit was most consistent for eye configuration, with some patients performing normally for mouth configuration. Patients with anterior temporal lesions had better configuration perception, though at least one patient showed a more subtle failure to integrate configural data from different facial regions. Facial imagery, an index of facial memories, was severely impaired by bilateral lesions that included the right anterior temporal lobe and marginally impaired by fusiform lesions alone; unilateral right fusiform lesions tended to spare imagery for facial features. These findings suggest that (I) prosopagnosia is more severe with bilateral than unilateral lesions, indicating a minor contribution of the left hemisphere to face recognition, (2) perception of facial configuration critically involves the right fusiform gyrus and (3) access to facial memories is most disrupted by bilateral lesions that also include the right anterior temporal lobe. This supports assertions that more apperceptive variants of prosopagnosia are linked to fusiform damage, whereas more associative variants are linked to anterior temporal damage. Next, we found that behavioural indices of covert recognition correlated with measures of overt familiarity, consistent with theories that covert behaviour emerges from the output of damaged neural networks, rather than alternative pathways. Finally, to probe the face specificity of the prosopagnosic defect, we tested recognition of fruits and vegetables: While face specificity was not found in most of our patients, the data of one patient suggested that this may be possible with more focal lesions of the right fusiform gyrus.

low-level laser therapy applied transcranially to mice following traumatic brain injury significantly reduces long-term neurological deficits.

Low-level laser therapy (LLLT) has been evaluated in this study as a potential therapy for traumatic brain injury (TBI). LLLT has been found to modulate various biological processes. Following TBI in mice, we assessed the hypothesis that LLLT might have a beneficial effect on their neurobehavioral and histological outcome. TBI was induced by a weight-drop device, and motor function was assessed 1 h post-trauma using a neurological severity score (NSS). Mice were then divided into three groups of eight mice each: one control group that received a sham LLLT procedure and was not irradiated; and two groups that received LLLT at two different doses (10 and 20 mW/cm(2) ) transcranially. An 808-nm Ga-As diode laser was employed transcranially 4 h post-trauma to illuminate the entire cortex of the brain. Motor function was assessed up to 4 weeks, and lesion volume was measured. There were no significant changes in NSS at 24 and 48 h between the laser-treated and non-treated mice. Yet, from 5 days and up to 28 days, the NSS of the laser-treated mice were significantly lower (p < 0.05) than the traumatized control mice that were not treated with the laser. The lesion volume of the laser treated mice was significantly lower (1.4%) than the non-treated group (12.1%). Our data suggest that a non-invasive transcranial application of LLLT given 4 h following TBI provides a significant long-term functional neurological benefit. Further confirmatory trials are warranted.

D-cycloserine improves functional recovery and reinstates long-term potentiation (LTP) in a mouse model of closed head injury.

Traumatic brain injury triggers a massive glutamate efflux, activation of NMDA receptor channels, and cell death. Recently, we reported that NMDA receptors in mice are down-regulated from hours to days following closed head injury (CHI), and treatment with NMDA improved recovery of motor and cognitive functions up to 14 d post-injury. Here we show that a single injection of a low dose of D-cycloserine (DCS), a partial NMDA receptor agonist, in CHI mice 24 h post-injury, resulted in a faster and greater recovery of motor and memory functions as assessed by neurological severity score and object recognition tests, respectively. Moreover, DCS treatment of CHI mice led to a significant improvement of hippocampal long-term potentiation (LTP) in the CA1 region that was completely blunted in CHI control mice. However, DCS did not improve CHI-induced impairment in synaptic glutamate release measured by paired pulse facilitation (PPF) ratio in hippocampal CA1 region. Finally, CHI-induced reduction of brain-derived neurotrophic factor (BDNF) was fully restored following DCS treatment. Since DCS is in clinical use for other indications, the present study offers a novel approach to treat human brain injury.

Meditation: a new role for an old friend.

Meditation has been a spiritual and healing tradition for centuries. In 1972, Keith Wallace and Herbert Benson published a landmark article looking at meditation from a scientific perspective. The author reviewed their article, plus selected scientific literature on meditation since that time, to see if there was enough evidence to warrant the inclusion of meditation in the treatment protocols of serious disease. This review, plus an illustrative case study, demonstrated that such inclusion is warranted and further research is necessary.

Characterization of memory impairment following closed-head injury in children using the Rey Auditory Verbal Learning Test (AVLT).

Memory impairment following closed-head injury (CHI) in children is well documented. Characterization of the memory deficits of children with CHI could contribute to the prediction of academic performance and rehabilitation of these children. Twenty-five children who sustained closed-head injury and 25 matched controls were administered the Rey Auditory Verbal Learning Test (AVLT). The advantage of this memory test is that a number of memory components are measured simultaneously, thus enabling us to study the relations between different aspects of memory within the same patient sample. The findings indicate that the Rey AVLT is a good test for characterization of impaired verbal memory in children following CHI. Transformation of scores derived from the Rey AVLT to Z-scores enables us to determine the relative effect of CHI in children on different memory scores. Raw scores were more vulnerable than relational ones, derived as the difference between two raw scores (e.g., learning, Trial 5 - 1), to closed-head injury in children, and scores reflecting word span were the least vulnerable. The results are discussed in terms of the possible contribution of the frontal lobes, which are frequently affected in closed-head injuries, to memory performance.

The purpose of lexical/sublexical interaction during spelling: further evidence from dysgraphia and articulatory suppression.

We investigated how the lexical and sublexical processes interact in spelling using an articulatory suppression task to disrupt the sublexical process in a dysgraphic patient (JDO). Using a similar task, Folk et al. (2002) found evidence that the sublexical process interacts with the lexical process by strengthening a target word's graphemes. We replicated the findings of Folk et al. in a patient with a more severe deficit to the lexical process. We compared the error patterns produced under normal spelling conditions versus spelling during articulatory suppression and found an increase in lexical substitution errors ("thaw"-->T-H-O-U-G-H) under articulatory suppression. These findings indicate that by strengthening a target word's graphemes, the sublexical process helps to create an advantage for a target word over form-related word neighbours that compete with it for output.