Effects of Nimodipine and Nigella sativa on Oxidative Stress and Apoptosis in Serum and Brain Tissue of Rats with Experimental Head Trauma.

AIM: To investigate whether Nimodipine (N) and Nigella sativa (NS) oil have protective, antioxidant effects in brain injury caused by experimental head trauma. MATERIAL AND METHODS: Fifty albino Wistar rats were randomly divided into 5 groups that underwent experimental head trauma. Oxidative parameters were compared in the serum and brain tissue of the different groups. In addition, apoptosis and caspase-3 immunoreactivity were evaluated by histopathological examination. RESULTS: Serum total antioxidant status (TAS) levels were significantly increased in N and N+NS groups when compared with controls (p=0.001, p < 0.01). Tissue TAS levels were significantly higher in the NS and N+NS groups compared to controls (p=0.001, p < 0.01). Total oxidant status levels in the brain tissue were significantly higher in the NS group than in the control group (p=0.021). CONCLUSION: N and NS were shown to significantly reduce the occurrence of oxidative stress in secondary brain injury due to head trauma. We also found that apoptosis levels decreased in response to N, NS and N+NS treatments after head trauma.

The King-Devick test in mixed martial arts: the immediate consequences of knock-outs, technical knock-outs, and chokes on brain functions.

The aim of this prospective cohort study was to determine the effect of an 'event,' defined as a knock-out (KO), technical knock-out (TKO), choke, or submission, on King-Devick (K-D) test times in mixed martial arts (MMA) athletes. MMA athletes (28.3 ± 6.6 years, n = 92) underwent K-D testing prior to and following a workout or match. Comparison of baseline and post-workout/match K-D times to assess any significant change. K-D tests worsened (longer) in a majority of athletes following an 'event' (N = 21) (49.6 ± 7.8 s vs 46.6 ± 7.8 s, p = 0.0156, Wilcoxon signed-rank test). K-D tests improved (shorter) following a standard workout or match in which no 'event' occurred in a majority of cases (n = 69) (44.2 ± 7.2 s vs 49.2 ± 10.9 s, p = <0.0001, Wilcoxon signed-rank test). Longer duration (worsening) of post-match K-D tests occurred in most athletes sustaining an 'event'; K-D tests shortened (improved) in a majority of athletes not sustaining an 'event'. Our study suggests MMA athletes suffering an 'event' may have sustained a brain injury similar to a concussion.

Dietary Zinc Modulates Matrix Metalloproteinases in Traumatic Brain Injury.

Animal models of mild traumatic brain injury (mTBI) provide opportunity to examine the extent to which dietary interventions can be used to improve recovery after injury. Animal studies also suggest that matrix metalloproteinases (MMPs) play a role in tissue remodeling post-TBI. Because dietary zinc (Zn) improved recovery in nonblast mTBI models, and the MMPs are Zn-requiring enzymes, we evaluated the effects of low- (LoZn) and adequate-Zn (AdZn) diets on MMP expression and behavioral responses, subsequent to exposure to a single blast. MMP messenger RNA expression in soleus muscle and frontal cortex tissues were quantified at 48 h and 14 days post-blast. In muscle, blast resulted in significant upregulation of membrane-type (MT)-MMP, MMP-2, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 at 48 h post-injury in rats consuming AdZn. At 14 days post-blast, there were no blast or dietary effects observed on MMP levels in muscle, supporting the existence of a Zn-responsive, functional repair and remodeling mechanism. In contrast, blast resulted in a significant downregulation of MT-MMP, TIMP-1, and TIMP-2 and a significant upregulation of MMP-3 levels at 48 h post-injury in cortex tissue, whereas at 14 days post-blast, MT-MMP, MMP-2, and TIMP-2 were all downregulated in response to blast, independent of diet, and TIMP-1 were significantly increased in rats fed AdZn diets despite the absence of elevated MMPs. Because the blast injuries occurred while animals were under general anesthesia, the increased immobility observed post-injury in rats consuming LoZn diets suggest that blast mTBI can, in the absence of any psychological stressor, induce post-traumatic stress disorder-related traits that are chronic, but responsive to diet. Taken together, our results support a relationship between marginally Zn-deficient status and a compromised regenerative response post-injury in muscle, likely through the MMP pathway. However, in neuronal tissue, changes in MMP/TIMP levels after blast indicate a variable response to marginally Zn-deficient diets that may help explain compromised repair mechanism(s) previously associated with the systemic hypozincemia that develops in patients with TBI.

Nano-Pulsed Laser Therapy Is Neuroprotective in a Rat Model of Blast-Induced Neurotrauma.

We have developed a novel, non-invasive nano-pulsed laser therapy (NPLT) system that combines the benefits of near-infrared laser light (808 nm) and ultrasound (optoacoustic) waves, which are generated with each short laser pulse within the tissue. We tested NPLT in a rat model of blast-induced neurotrauma (BINT) to determine whether transcranial application of NPLT provides neuroprotective effects. The laser pulses were applied on the intact rat head 1 h after injury using a specially developed fiber-optic system. Vestibulomotor function was assessed on post-injury days (PIDs) 1-3 on the beam balance and beam walking tasks. Cognitive function was assessed on PIDs 6-10 using a working memory Morris water maze (MWM) test. BDNF and caspase-3 messenger RNA (mRNA) expression was measured by quantitative real-time PCR (qRT-PCR) in laser-captured cortical neurons. Microglia activation and neuronal injury were assessed in brain sections by immunofluorescence using specific antibodies against CD68 and active caspase-3, respectively. In the vestibulomotor and cognitive (MWM) tests, NPLT-treated animals performed significantly better than the untreated blast group and similarly to sham animals. NPLT upregulated mRNA encoding BDNF and downregulated the pro-apoptotic protein caspase-3 in cortical neurons. Immunofluorescence demonstrated that NPLT inhibited microglia activation and reduced the number of cortical neurons expressing activated caspase-3. NPLT also increased expression of BDNF in the hippocampus and the number of proliferating progenitor cells in the dentate gyrus. Our data demonstrate a neuroprotective effect of NPLT and prompt further studies aimed to develop NPLT as a therapeutic intervention after traumatic brain injury (TBI).

I hurt so: hypnotic interventions and palliative care for traumatic brain injury.

This article presents a case study in which self-hypnosis, hypnosis-assisted psychotherapy, and palliative care strategies were provided within a multi-modal integrative treatment program for a 38-year-old woman with traumatic brain injury (TBI) secondary to motor vehicle accident. Self-hypnosis was helpful in anxiety reduction and pain management. Hypnosis-assisted psychotherapy was beneficial in de-sensitizing many post-traumatic memories, and in managing post-concussion pain, including neuropathic pain and post-traumatic migraine headaches. A variety of palliative care techniques and spiritual interventions were applied to enhance sleep, moderate cognitive deficits, and enhance quality of life.

Evidence for Acute Electrophysiological and Cognitive Changes Following Routine Soccer Heading.

INTRODUCTION: There is growing concern around the effects of concussion and sub-concussive impacts in sport. Routine game-play in soccer involves intentional and repeated head impacts through ball heading. Although heading is frequently cited as a risk to brain health, little data exist regarding the consequences of this activity. This study aims to assess the immediate outcomes of routine football heading using direct and sensitive measures of brain function. METHODS: Nineteen amateur football players (5 females; age 22±3y) headed machine-projected soccer balls at standardized speeds, modelling routine soccer practice. The primary outcome measure of corticomotor inhibition measured using transcranial magnetic stimulation, was assessed prior to heading and repeated immediately, 24h, 48h and 2weeks post-heading. Secondary outcome measures were cortical excitability, postural control, and cognitive function. RESULTS: Immediately following heading an increase in corticomotor inhibition was detected; further to these electrophysiological alterations, measurable reduction memory function were also found. These acute changes appear transient, with values normalizing 24h post-heading. DISCUSSION: Sub-concussive head impacts routine in soccer heading are associated with immediate, measurable electrophysiological and cognitive impairments. Although these changes in brain function were transient, these effects may signal direct consequences of routine soccer heading on (long-term) brain health which requires further study.

Phenotypic Screening of Small-Molecule Inhibitors: Implications for Therapeutic Discovery and Drug Target Development in Traumatic Brain Injury.

The inability of central nervous system (CNS) neurons to regenerate damaged axons and dendrites following traumatic brain injury (TBI) creates a substantial obstacle for functional recovery. Apoptotic cell death, deposition of scar tissue, and growth-repressive molecules produced by glia further complicate the problem and make it challenging for re-growing axons to extend across injury sites. To date, there are no approved drugs for the treatment of TBI, accentuating the need for relevant leads. Cell-based and organotypic bioassays can better mimic outcomes within the native CNS microenvironment than target-based screening methods and thus should speed the discovery of therapeutic agents that induce axon or dendrite regeneration. Additionally, when used to screen focused chemical libraries such as small-molecule protein kinase inhibitors, these assays can help elucidate molecular mechanisms involved in neurite outgrowth and regeneration as well as identify novel drug targets. Here, we describe a phenotypic cellular (high content) screening assay that utilizes brain-derived primary neurons for screening small-molecule chemical libraries.

Differences in Cognitive Function of Rats with Traumatic Brain Injuries Following Hyperbaric Oxygen Therapy.

BACKGROUND Hyperbaric oxygen (HBO) is a historical therapeutic option in the treatment of various types of brain damage. At present, clinical treatment of hypoxic-ischemic injury is giving priority to cognitive training. The effects of HBO on cognitive dysfunction were observed in a controlled cortical impact (CCI) rat model. MATERIAL AND METHODS Seventy male SD rats were randomly divided into control (n=10) and intervention (n=60) groups. All rats underwent baseline water maze testing 1 day before modeling, and were retested 8 weeks after modeling. The percentage of residence time during escape latency in the target quadrant and the total time were recorded. Data were analyzed by SPSS 16.0 software. P<0.05 was considered statistically significant. RESULTS After 8 weeks, no statistical difference (P>0.05) existed in spatial learning ability in the 3-day and 5-day groups when compared with baseline. The other groups were statistically different by auto-comparison (P<0.05). No statistical difference (P>0.05) in spatial memory existed in the 5-day and 1-week groups when compared with baseline, while a significant difference was noted in the other groups by self-comparison (P<0.05). No statistical difference (P>0.05) was noted in the level of expression of growth-associated protein-43 (GAP-43) and synaptophysin (Syn) in the 1-day group compared with the control group. The remaining groups and the control group were statistically different (P<0.05), while the level of expression of GAP-43 and Syn in the 5-day, 1-week, and 2-week groups was significantly different compared with that in the control group (P<0.01). CONCLUSIONS If HBO therapy was provided 5-7 days after craniocerebral trauma, there was apparent improvement in cognitive function and neuroplasticity.

Eficacia del oxígeno hiperbárico en el tratamiento de la radionecrosis y el edemacerebral sintomáticos tras radiocirugía con acelerador lineal / Usefulness of hyperbaric oxygen in the treatment of radionecrosis and symptomatic brain edema after LINAC radiosurgery

La radio necrosis y el edema cerebral son complicaciones asociadas a la radiocirugía. Presentamos los casos de tres pacientes tratadas con radiocirugía mediante acelerador lineal, de un meningioma de polo frontal izquierdo, peñasco y para sagital parietooccipital, respectivamente, que desarrollaron, entre dos y ocho meses más tarde, lesiones de tipo radio necrótico con extenso edema peritumoral que resultaron resistentes al tratamiento con esteroides y que se han resuelto con la administración de 40 sesiones de oxígeno hiperbárico. Son pocos los casos publicados hasta ahora en la literatura con tan excelentes resultados, por lo que consideramos un hecho a tener muy en cuenta ante las posibles complicaciones de este tipo que puedan presentarse en el transcurso de la práctica radioquirúrgica antes de recurrir a la cirugía (AU)

Radionecrosis with brain edema is a complication of radiosurgery. Three female patients harbouring a frontal pole, petrous and parasagital parietoocipital meningiomas respectively who had been treated with LINAC radiosurgery are presented. Those patients developed, between two and eight months later, a severe symptomatic radionecrosis with a huge brain edema resistant to the usual steroid therapy. Only after 40 sessions of hyperbaric oxygen, a good remission of the lesions was obtained. There are few cases reported in the literature with such a good outcome. Consequentely, this therapy must be taken into account to treat this type of radiosurgical complication before considering surgery (AU)