Effects of Repetitive Transcranial Magnetic Stimulation on Behavioral Recovery during Early Stage of Traumatic Brain Injury in Rats

Repetitive transcranial magnetic stimulation (rTMS) is a promising technique that modulates neural networks. However, there were few studies evaluating the effects of rTMS in traumatic brain injury (TBI). Herein, we assessed the effectiveness of rTMS on behavioral recovery and metabolic changes using brain magnetic resonance spectroscopy (MRS) in a rat model of TBI. We also evaluated the safety of rTMS by measuring brain swelling with brain magnetic resonance imaging (MRI). Twenty male Sprague-Dawley rats underwent lateral fluid percussion and were randomly assigned to the sham (n=10) or the rTMS (n=10) group. rTMS was applied on the fourth day after TBI and consisted of 10 daily sessions for 2 weeks with 10 Hz frequency (total pulses=3,000). Although the rTMS group showed an anti-apoptotic effect around the peri-lesional area, functional improvements were not significantly different between the two groups. Additionally, rTMS did not modulate brain metabolites in MRS, nor was there any change of brain lesion or edema after magnetic stimulation. These data suggest that rTMS did not have beneficial effects on motor recovery during early stages of TBI, although an anti-apoptosis was observed in the peri-lesional area.     

Astrocytes‐derived exosomes induce neuronal recovery after traumatic brain injury via delivering gap junction alpha 1‐20 k

Astrocytes are more resistant to ischemia and hypoxia in the acute phase of brain injury after traumatic brain injury (TBI). Previous study showed that gap junction alpha 1 (GJA1) phosphorylation can increase the survival of damaged astrocytes. The GJA1‐20 k expression in neurons co‐culture with astrocytes was positively correlated with exosomes uptake. This study aims to explore the effect of exogenous GJA1‐20 k carried by astrocyte‐derived exosomes on neurons apoptosis and mitochondrial function after TBI. Astrocytes were co‐cultured with the neuron with/without damage from air pressure. Exosomes were isolated, extracted from the culture medium by differential ultra‐centrifugation, and verified by electron microscopy. Immunofluorescence staining, tunnel, western blot were employed to detect exosomes marker CD60, apoptosis, and mitochondrial function related protein expression and GJA1‐20 k in cell culture. A rat model of hydraulic injury TBI was built, and exosomes was transferred. 2,3,5‐Triphenyltetrazolium chloride (TTC) staining and immunohistochemistry staining of Nissl and microtubule associated protein 2 were used to detect the brain damage. A transwell stereo culture model of astrocytes and TBI‐like injured neuron was constructed. The exosomes derived from astrocytes promoted the recovery of damaged neuron by in vitro exosome treatment. Compared with GJA1‐20 k knockout exosome control group, GJA1‐20 k exosomes were uptaken by neuron and downregulated the apoptosis rate and upregulated mitochondrial function to promote neuronal recovery. Finally, the results were validated by TTC staining and damaged tissue sections of rat TBI model. This study contributes to a better understanding of the astrocyte‐neuron protection mechanism in TBI and provides a potential new target for the treatment of TBI.     

Cluster Analysis of Vulnerable Groups in Acute Traumatic Brain Injury Rehabilitation

Objective

To analyze the complex relation between various social indicators that contribute to socioeconomic status and health care barriers.

Feasibility and Preliminary Validation of an Online Version of the Ohio State University Traumatic Brain Injury Identification Method

Objective

To test the feasibility and validity of an online version of an established interview designed to determine a lifetime history of traumatic brain injury (TBI).

Influence of Self-Efficacy and Coping on Quality of Life and Social Participation After Acquired Brain Injury: A 1-Year Follow-Up Study

ObjectivesTo investigate the relations linking self-efficacy and coping to quality of life (QOL) and social participation and what effect self-efficacy, changes in self-efficacy, and coping style have on long-term QOL and social participation.DesignProspective clinical cohort study.SettingGeneral hospitals, rehabilitation centers.ParticipantsPatients with newly acquired brain injury (ABI) (N=148) were assessed at baseline (start outpatient rehabilitation or discharge hospital/inpatient rehabilitation; mean time since injury, 15wk) and 1 year later (mean time since injury, 67wk).InterventionsNot applicable.Main Outcome MeasuresQOL was measured with the EuroQuol 5D (the EQ-5D index and the EQ-5D visual analog scale [EQ VAS]) and the 9-item Life Satisfaction Questionnaire (LiSat-9), social participation with the modified Frenchay Activities Index, coping with the Coping Inventory for Stressful Situations, and self-efficacy with the Traumatic Brain Injury Self-efficacy Questionnaire.ResultsAt baseline, self-efficacy moderated the effect of emotion-oriented coping on the EQ-5D index and of avoidance coping on the EQ VAS. Self-efficacy mediated the relation between emotion-oriented coping and LiSat-9. An increase in self-efficacy over time predicted better scores on the EQ-5D index (β=.30), the EQ VAS (β=.49), and LiSat-9 (β=.44) at follow-up. In addition, higher initial self-efficacy (β=.40) predicted higher LiSat-9 scores at follow-up; higher initial emotion-oriented coping (β=−.23) predicted lower EQ VAS scores at follow-up. Higher modified Frenchay Activities Index scores at follow-up were predicted by higher self-efficacy (β=.19) and higher task-oriented coping (β=.14) at baseline (combined R²=5.1%).ConclusionsSelf-efficacy and coping predict long-term QOL but seem less important in long-term social participation. High self-efficacy protects against the negative effect of emotion-oriented coping. Enhancing self-efficacy in the early stage after ABI may have beneficial long-term effects.     

Recovery Over 6 Months of Medical Decision-Making Capacity After Traumatic Brain Injury

ObjectiveTo investigate recovery of medical decision-making capacity (MDC) over 6 months in persons with traumatic brain injury (TBI) stratified by injury severity.DesignLongitudinal study comparing controls and patients with TBI 1 month after injury (t1) and 6 months after injury (t2).SettingInpatient TBI rehabilitation unit and outpatient neurology department.ParticipantsParticipants (N=151) consisted of control subjects (n=60) and patients with TBI (n=91) stratified by injury severity: mild TBI (mTBI; n=27), complicated mild TBI (cmTBI; n=20), and moderate/severe TBI (msevTBI; n=44).InterventionsNot applicable.Main Outcome MeasuresWe used the Capacity to Consent to Treatment Instrument to evaluate MDC performance on 5 consent standards (expressing choice, reasonable choice, appreciation, reasoning, and understanding). We also assigned capacity impairment ratings on the consent standards to each participant with TBI using cut scores referenced to control performance.ResultsControl performance was stable across time on the consent standards. Patients with mTBI and cmTBI performed below controls on the understanding standard at t1 but not t2. Patients with msevTBI performed below controls on appreciation, reasoning, and understanding at t1, and on appreciation and understanding at t2, but showed substantial improvement over time.ConclusionsRegardless of injury severity, all groups with TBI demonstrated baseline impairment of MDC with subsequent partial or full recovery of MDC over a 6-month period. However, a sizeable proportion of individual patients with TBI in each group continued to demonstrate capacity compromise at 6 months postinjury. Clinically, this finding suggests that individuals with TBI, regardless of injury severity, need continued monitoring regarding MDC for at least 6 months after injury.     

Total body irradiation: Significant dose sparing of lung tissue achievable by helical tomotherapy

PurposeTotal body irradiation (TBI) is an important procedure in the conditioning for bone marrow and hematopoietic stem cell transplantation. Doses up to 12 Gy are delivered in hyperfractionated regimes. TBI performed with helical Tomotherapy® (Accuray, Madison, Wisconsin, USA) is an alternative to conventional techniques to deliver dose in extended target volumes with the possibility of simultaneous dose sparing to organs at risk. In this study we focused on maximum dose reduction to the lungs in TBI using helical Tomotherapy®.Material and methodsForty treatment plans of patients who received TBI were calculated with TomoH® (Accuray, Madison, Wisconsin, USA, Version 2.0.4) with a dose of 12 Gy delivered in six equal fractions (2 × 2 Gy/day). Planning iterations necessary to accomplish ICRU 83 report should be less than 250. Treatment time should be practicable in daily routine (<60 min.). Besides the usual contouring of organs at risk special contouring was required for optimization processes which focused on maximum dose sparing in the central lung tissue. Dose constraints (D2, D98, D99) were predefined for target volumes (i.e. PTV TBI D99: 90% of prescribed dose). Homogeneity index <0.15 was defined for acceptability of the treatment plan.ResultsFor all patients acceptable treatment plan fulfilling the predefined constraints were achievable. An average time of 46 min is required for treatment. Thirty-four of forty patients fulfilled D2 in the PTV TBI. Four patients failed D2 due to a high BMI >28 (maximum dose 13.76 Gy = 114.7%). The D98 in the PTV TBI was not reached by 2/40 patients due to BMI > 31 (minimum dose 11.31 Gy = dose coverage of 94.2%). Also these two patients failed the homogeneity index <0.15. The mean lung dose over all patients of the right lung was 7.18 Gy (range 6.4–9.5 Gy). The left lung showed a median (D50) dose of 7.9 Gy (range 6.7–9.3 Gy). Central lung dose showed a mean dose (D50) of 5.16 Gy (range 4.02–7.29 Gy). The D80 of the central lung showed an average dose of 3.87 Gy.ConclusionsTotal body irradiation using helical Tomotherapy® can be delivered with maximum lung tissue sparing (<6 Gy) but without compromise in adjacent PTV TBI structures (i.e. ribs, heart). High conformity and homogeneity in extended radiation volumes can be reached with this technique in an acceptable planning and treatment time. Limitations may occurred in patients with high body mass index.     

Total body irradiation using Helical Tomotherapy®: Treatment technique,dosimetric results and initial clinical experience

Purpose

Helical TomoTherapy^® allows precise and homogeneous tumour coverage and excellent sparing of organs at risk. We present here our treatment technique, dosimetric results, and our first clinical data for patients receiving total body irradiation as part of the conditioning regimen before hematopoietic stem cell transplantation.