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Cell-based therapy for traumatic brain injury.

ABSTRACT: Traumatic brain injury is a major economic burden to hospitals in terms of emergency department visits, hospitalizations, and utilization of intensive care units. Current guidelines for the management of severe traumatic brain injuries are primarily supportive, with an emphasis on surveillance (i.e. intracranial pressure) and preventive measures to reduce morbidity and mortality. There are no direct effective therapies available. Over the last fifteen years, pre-clinical studies in regenerative medicine utilizing cell-based therapy have generated enthusiasm as a possible treatment option for traumatic brain injury. In these studies, stem cells and progenitor cells were shown to migrate into the injured brain and proliferate, exerting protective effects through possible cell replacement, gene and protein transfer, and release of anti-inflammatory and growth factors. In this work, we reviewed the pathophysiological mechanisms of traumatic brain injury, the biological rationale for using stem cells and progenitor cells, and the results of clinical trials using cell-based therapy for traumatic brain injury. Although the benefits of cell-based therapy have been clearly demonstrated in pre-clinical studies, some questions remain regarding the biological mechanisms of repair and safety, dose, route and timing of cell delivery, which ultimately will determine its optimal clinical use.

SUBMITTER: Gennai S

PROVIDER: S-EPMC4500763 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Cell-based therapy for traumatic brain injury.

Gennai S S Monsel A A Hao Q Q Liu J J Gudapati V V Barbier E L EL Lee J W JW Lee J W JW

British journal of anaesthesia 20150801 2

Traumatic brain injury is a major economic burden to hospitals in terms of emergency department visits, hospitalizations, and utilization of intensive care units. Current guidelines for the management of severe traumatic brain injuries are primarily supportive, with an emphasis on surveillance (i.e. intracranial pressure) and preventive measures to reduce morbidity and mortality. There are no direct effective therapies available. Over the last fifteen years, pre-clinical studies in regenerative ...[more]

PMID: 26170348

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Project description:All work was performed at the Barrow Neurological Institute at Phoenix Children's Hospital. Objective: Investigate injury severity, neuroimaging, physiology, and outcomes with bolus hyperosmolar therapy (HT) of 3% hypertonic saline or mannitol. Methods: Retrospective cohort analysis was performed. Physiologic variables included intracranial pressure (ICP), arterial blood pressure (ABP), and heart rate (HR). Volume-pressure compensation (PVC) indices included ICP pulse amplitude (AMP) and correlation of AMP and ICP (RAP). Cerebrovascular pressure reactivity (CVPR) indices included pressure reactivity index (PRx), pulse amplitude index (PAx), wavelet PRx (wPRx), and correlation of AMP and cerebral perfusion pressure (RAC). Heart rate variability (HRV) indices included heart rate standard deviation (HRsd), heart rate root mean square of successive differences (HRrmssd) and low-high frequency ratio (LHF). Outcome was assessed using Glasgow Outcomes Scale Extended Pediatrics, 12-months post-injury. Generalized estimating equations was applied to investigate associations of physiologic changes and pre-treatment indices with HT efficacy. Repeated measures analysis of variance was applied to investigate changes after HT without intracranial hypertension (ICH). Wilcoxon rank-sum was applied to investigate HT responsiveness with age, injury severity, neuroimaging, and outcomes. Results: Thirty children received bolus HT. ICH reduction after HT was associated with reduced ICP (p = 0.0064), ABP (p = 0.0126), PRx (p = 0.0063), increased HRsd (p = 0.0408), and decreased pretreatment RAC (p = 0.0115) and wPRx (p = 0.0072). HT-responsive patients were older and had improved outcomes (p = 0.0394). HT without ICH was associated with increased ICP (P < 0.0001) and ABP (P < 0.0001), increases in all HRV indices and decreases in all PVC indices. Conclusion: After pediatric TBI, efficacious HT is associated with decreased ICP and ABP, pre-treatment indices suggesting efficient CVPR, and potentially improved outcomes.

Project description:Background and Objectives: Fatigue and sleep disturbance negatively impact quality of life following brain injury and there are no established treatments. Building on research showing efficacy of blue light therapy delivered via a lightbox in reducing fatigue and daytime sleepiness after traumatic brain injury (TBI), this paper describes the development and implementation of a novel in-home light therapy to alleviate fatigue and sleep disturbance in two case studies. Methods: During the 8-week lighting intervention, participants' home lighting was adjusted to provide high intensity, blue-enriched (high melanopic) light all day as a stimulant and dimmer, blue-depleted (low melanopic) light for 3 h before sleep as a soporific. The sham 8-week control condition resembled participants' usual (baseline) lighting conditions (3,000-4,000 K all day). Lighting conditions were crossed-over. Outcomes were measures of fatigue, subjective daytime sleepiness, sleep quality, insomnia symptoms, psychomotor vigilance and mood. Case study participants were a 35-year old male (5 years post-TBI), and a 46-year-old female (22 years post-TBI). Results: The relative proportion of melanopic lux was greater in Treatment lighting than Control during daytime, and lower during evenings. Participants found treatment to be feasible to implement, and was well-tolerated with no serious side effects noted. Self-reported compliance was >70%. Both cases demonstrated reduced fatigue, sleep disturbance and insomnia symptoms during the treatment lighting intervention. Case 2 additionally showed reductions in daytime sleepiness and depressive symptoms. As expected, symptoms trended toward baseline levels during the control condition. Discussion: Treatment was positively received and compliance rates were high, with no problematic side-effects. Participants expressed interest in continuing the ambient light therapy in their daily lives. Conclusions: These cases studies demonstrate the acceptability and feasibility of implementing a personalized in-home dynamic light treatment for TBI patients, with evidence for efficacy in reducing fatigue and sleep disturbance. Clinical Trial Registration:www.anzctr.org.au, identifier: ACTRN12617000866303.

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Cell-based therapy for traumatic brain injury.

Publications

Cell-based therapy for traumatic brain injury.

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