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Hyaluronic acid-poly-D-lysine-based three-dimensional hydrogel for traumatic brain injury.

Brain tissue engineering in the postinjury brain represents a promising option for cellular replacement and rescue, providing a cell scaffold for either transplanted or resident cells. In this article, a hyaluronic acid (HA)-poly-D-lysine (PDL) copolymer hydrogel with an open porous structure and viscoelastic properties similar to neural tissue has been developed for brain tissue engineering. The chemicophysical properties of the hydrogel with HA:PDL ratios of 10:1, 5:1, and 4:1 were investigated by scanning electron microscopy (SEM) and X-ray photoelectron spectrometry. Neural cells cultured in the hydrogel were studied by phase-contrast microscope and SEM. The incorporation of PDL peptides into the HA-PDL hydrogel allowed for the modulation of neuronal cell adhesion and neural network formation. Macrophages and multinucleated foreign body giant cells found at the site of implantation of the hydrogel in the rat brain within the first weeks postimplantation decreased in numbers after 6 weeks, consistent with the host response to inert implants in numerous tissues. Of importance was the infiltration of the hydrogel by glial fibrillary acidic protein-positive cells-reactive astrocytes-by immunohistochemistry and the contiguity between the hydrogel and the surrounding tissue demonstrated by SEM. These findings indicated the compatibility of this hydrogel with brain tissue. Collectively, the results demonstrate the promise of an HA-PDL hydrogel as a scaffold material for the repair of defects in the brain.

Animals↗

Expression of cysteinyl leukotriene receptor 1 in human traumatic brain injury and brain tumors.

Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators. CysLT receptor 1 (CysLT(1)) is one of the two CysLT receptors that has been cloned. Although the expression of CysLT(1) in the brain has been demonstrated by Northern blot and RT-PCR analyses, the location of CysLT(1) in the brain remains unknown. The objective of this study was to examine the distribution of CysLT(1) by immunohistochemical analysis in human brains with traumatic injury or tumors. CysLT(1) was expressed intensely in the microvascular endothelial cells in both normal and abnormal conditions. At 8 days after traumatic injury, microvascular regeneration was found and all of the endothelial cells highly expressed CysLT(1). In gray and white matters of the normal regions of the brain, CysLT(1) was expressed weekly or not at all. However, the CysLT(1) expression increased in the neuron- and glial-appearing cells in gray and white matters after traumatic brain injury. CysLT(1) was also detected in astrocytoma, ganglioglioma and metastatic adenocarcinoma, and the expression in the neuron- and glial-appearing cells around brain tumors increased robustly.

Adult↗

Neurobehavioral outcome of children's mild traumatic brain injury.

Brain damage is underestimated as a public health and personal problem. The common belief in a good prognosis for childhood brain damage is unsubstantiated. It is based on lack of rigorous study and examiner satisfaction with a low response level. Occult brain trauma plagues victims into maturity. Above a rather low threshold of injury (even without focal neurologic findings), cognitive, personality, and adaptive dysfunctions are common and impairing. Child abuse signals were described. Brain lesions impair both matured functions and those expressed later. Dysfunctions were discussed for these neurobehavioral systems: consciousness, attention and tonic motor level; sensorimotor and body schema; neurophysiologic; cerebral personality; intelligence; memory; language; information processing; posttraumatic stress and mood; identity and insight; adaptivity in the community. Outcome evolves from complex pathologic, neurologic, anatomic, and personality parameters, the postinjury interval and child's age, the maturity and developmental trajectory of the function, social support, and emotional reaction to impairment. Assessment should study the entire range of functions, utilizing records, collaterals, observation, and qualitative and psychometric measurement. Complex, challenging, and ecologically relevant tasks are appropriate. There are several patterns of outcome: immediate permanent deficits; improvement through compensatory mechanisms, but with subclinical deficits; and initial progress with delayed expression (premature plateau of cognitive and personality maturity; physiologic developmental deficits). Confirmation of mild TBI may require several years of observation to determine late dysfunctions and deviation from preinjury or postinjury performance or expected level of development.

Behavior↗

Long-term multi-dimensional outcome following isolated traumatic brain injuries and traumatic brain injuries associated with multiple trauma.

We retrospectively investigated long-term, multi-dimensional quality-of-life outcomes in 68 male patients who suffered pure head injuries and 63 male head-injured patients with associated multiple trauma. Results indicated that patients sustaining associated multiple trauma were significantly younger and more deeply comatose on admission. Trends were found to suggest that patients sustaining associated multiple trauma also remain in coma longer, and experience more difficulties in social interaction and overall psychosocial functioning, but less difficulties in mobility compared with pure-head-injured patients. These findings should be taken into account in the evaluation of results of treatment as well as in the planning and allocation of resources for head-injured patients.

Activities of Daily Living↗

Evaluation of designs for clinical trials of neuroprotective agents in head injury. European Brain Injury Consortium.

In a study involving the statistical modeling of potential head injury trials, we explore approaches to trial design that could enhance their power to detect treatment-related effects on clinical outcome. The study uses a survey organized by the European Brain Injury Consortium of over 1,000 head-injured patients to characterize the population from which trial participants can be selected. A variety of models are postulated for the effects of "neuroprotective" treatment on outcome, and their interaction with a range of strategies for targeting patients for inclusion in the trial is evaluated. A very simple strategy of targeting patients with an intermediate prognosis was found to allow a reduction in sample size by 30%, with no reduction in statistical power. This paper illustrates an important methodology for studying the characteristics of competing trial designs.

Adolescent↗

The synergistic effect of acute subdural hematoma combined with diffuse traumatic brain injury on brain edema.

It is well-documented that acute subdural hematoma (ASDH) following diffuse traumatic brain injury (dTBI) contributes to severe disability and high mortality. The objective of this study was to characterize edema formation in a model of ASDH and ASDH following dTBI. Eighteen Sprague-Dawley rats were separated into three groups: Sham operated (n = 6), ASDH (n = 6), ASDH following dTBI (n = 6). Diffuse TBI was produced via the Impact-Acceleration Model [10]. ASDH was induced in the left hemisphere using the well-described method [11]. Total tissue water content was determined 4 hours after TBI utilizing wet-weight/dry-weight assessment. Our results show that ASDH causes a significant increase in tissue water content in the left hemisphere (79.2 +/- 0.7%) compared with the contralateral hemisphere (78.5 +/- 0.5%, p = 0.009). Animals exposed to ASDH following dTBI had significantly greater edema formation than those with ASDH (right: 80.9 +/- 0.4%, left: 80.5 +/- 0.7, p = 0.008). There was no significant difference between the left and right hemisphere. We conclude that edema formation in ASDH is worsened by the combination of dTBI and ASDH. Furthermore a diffuse and focal injury in combination retain the features of the diffuse injury, but with increased severity. Further studies are required to elucidate the synergistic mechanisms involved in these pathological processes.

Animals↗

[Permanent registration of the energy transformation in patients with skull-brain injuries and brain tumors].

By means of a measuring device based on the principles of indirect calorimetry, long-term recording of energy transformation in patients with cerebral tumours and cerebral traumas is performed. Contrary to the conception that the catabolic state in the postoperative/posttraumatic period corresponds to a negative balance between requirement and enteral/parenteral supply, it appears that, as a rule, the energy requirement is only 1 to 1 1/2 times higher than under normal conditions. During long-term measurement, clinical phenomena that are characterized by increased muscular activity (seizures, extension automatisms, extreme psychomotor excitations) show a daily requirement of maximal 3,500 kcal. Considering the clearly lower requirement, the change of the catabolic state by a high-caloric intake (5,000 and 6,000 calories/day) can only be due to an effect on the regulation of the metabolic processes.

Basal Metabolism↗

Early indicators and contributors to psychological distress in relatives during rehabilitation following severe traumatic brain injury: findings from the Brain Injury Outcomes Study.

OBJECTIVES: To develop a multivariate model of the dynamic interactions among key variables associated with relative distress and disrupted family functioning after traumatic brain injury (TBI). PARTICIPANTS: A relative sample (parents, spouses, close others; n = 134) derived from a statewide cohort of people with TBI recruited to the multicenter Brain Injury Outcomes Study. SETTING: A consecutive series of referrals over a 2-year period to the 11 adult units of the Brain Injury Rehabilitation Program in New South Wales, Australia. MAIN OUTCOME MEASURES: Relative measures included General Health Questionnaire-28 (psychological distress), Family Assessment Device (family functioning), and BIOS Family Needs Questionnaire (perceived adequacy of support). The degree of impairment and level of participation of the person with TBI were assessed by the Mayo-Portland Adaptability Inventory and Sydney Psychosocial Reintegration Scale, respectively. ANALYSIS: Path analysis examined the varying contribution of impairment, participation, and support variables to both relative distress and disturbances in family functioning. RESULTS: The overall model accounted for substantial proportions of the variance in psychological distress and family functioning. Importantly, the distress experienced by relatives was not due to the direct impact of the neurobehavioral impairments, but the effect of these impairments was mediated by the degree of community participation achieved by the person with TBI. CONCLUSIONS: The model highlights the impact on families when the person with TBI experiences restrictions in participation. Clinically, a greater focus on the provision of respite or case management services may assist in reducing relative distress.

Adult↗

The value of the "worst" computed tomographic scan in clinical studies of moderate and severe head injury. European Brain Injury Consortium.

OBJECTIVE: Computed tomographic (CT) scanning can reveal the pattern and severity of structural brain damage after head injury. With the proliferation of CT scanners in general hospitals, and with improvements in patient transport, the interval from injury to the first CT scan is decreasing. The potential result is an "admission" scan missing an evolving and potentially operable lesion. Furthermore, the literature is confusing regarding the timing and coding of CT findings. We sought to establish the frequency of deterioration in CT appearance from an admission scan to subsequent scans and the prognostic significance of such deterioration. METHODS: In a survey organized by the European Brain Injury Consortium, data on initial severity, management, and subsequent outcome were gathered prospectively for 1005 patients with moderate or severe head injury admitted to one of 67 European neurosurgical units during a 3-month period in 1995. The findings of the initial and the final ("worst") CT scan were classified according to the Traumatic Coma Data Bank system and were related to outcome as assessed using the Glasgow Outcome Scale 6 months after injury. RESULTS: Data on an initial and a final CT scan were available for 897 patients; of these, 724 patients were assessed using the Glasgow Outcome Scale at 6 months. The initial CT findings were classified as a diffuse injury for 53% of the cohort, with 16% of these diffuse injuries demonstrating deterioration on a subsequent scan. In 56 (74%) of 76 deteriorations, the change was from a diffuse injury to a mass lesion. When the initial CT scan demonstrated a diffuse injury without swelling or shift, evolution to a mass lesion was associated with a statistically significant increase in the risk of an unfavorable outcome (62% versus 38%). When the initial scan demonstrated evidence of swelling or shift, there was a nonsignificant trend in the opposite direction, although the numbers were limited. CONCLUSION: When an admission CT scan demonstrates evidence of a diffuse injury, follow-up scans should be performed, because approximately one in six such patients will demonstrate significant CT evolution. In studies comparing series of head-injured patients, correspondence of timing of CT scans is necessary for valid comparison.

Brain Injuries↗

Distribution of cysteinyl leukotriene receptor 2 in human traumatic brain injury and brain tumors.

AIM: To determine the distribution of cysteinyl leukotriene receptor 2 (CysLT2), one of the cysteinyl leukotriene receptors, in human brains with traumatic injury and tumors. METHODS: Brain specimens were obtained from patients who underwent brain surgery. CysLT2 in brain tissues was examined using immunohistochemical analysis. RESULTS: CysLT2 was expressed in the smooth muscle cells (not in the endothelial cells) of arteries and veins. CysLT2 was also expressed in the granulocytes in both vessels and in the brain parenchyma. In addition, CysLT2 was detected in neuron- and glial-appearing cells in either the late stages of traumatic injury or in the area surrounding the tumors. Microvessels regenerated 8 d after trauma and CysLT2 expression was recorded in their endothelial cells. CONCLUSION: CysLT2 is distributed in vascular smooth muscle cells and granulocytes, and brain trauma and tumor can induce its expression in vascular endothelial cells and in a number of other cells.

Adolescent↗

Congenital and acquired brain injury. 5. Outcomes after acquired brain injury.

UNLABELLED: This self-directed learning module highlights several aspects of outcome after acquired brain injury rehabilitation. It is part of the chapter on brain injury rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. In this article, functional measures commonly used in rehabilitation are described, and their potential uses for various populations are discussed. Key physiologic factors that predict outcome for persons with different acquired brain injuries are identified. Variables that affect return to school and work are described, and the studies evaluating the effectiveness of brain injury rehabilitation programs in general, as well as their subcomponents, are also reviewed. OVERALL ARTICLE OBJECTIVES: (a) To describe variables that affect outcome after acquired brain injury and (b) to identify the outcome tools most appropriate for the patient populations and outcomes to be studied.

Brain Injuries↗

Calcium channel blockers for acute traumatic brain injury.

BACKGROUND: Acute traumatic brain injury is a major cause of death and disability. Calcium channel blockers have been used in an attempt to prevent cerebral vasospasm after injury, maintain blood flow to the brain and so prevent further damage. OBJECTIVES: To estimate the effects of calcium channel blockers in patients with acute traumatic brain injury and in a subgroup of brain injury patients with traumatic subarachnoid haemorrhage. SEARCH STRATEGY: Hand searching and electronic searching for randomized controlled trials available by October 1997. SELECTION CRITERIA: Randomized controlled trials in patients with all levels of severity of clinically diagnosed acute traumatic brain injury. DATA COLLECTION AND ANALYSIS: Two reviewers (JL and CG) independently assessed the identified studies for eligibility and extracted data from each study. Summary odds ratios were calculated using the Mantel-Haenszel method. MAIN RESULTS: Four RCTs were identified as eligible for inclusion in the systematic review. The effect of calcium channel blockers on the risk of death was reported in all RCTs. The pooled odds ratio for the four studies was 0.91 (95% confidence interval 0. 70 to 1.17). For the three RCTs that reported death and severe disability the pooled odds ratio was 0.85 (95% CI 0.68 to 1.07). In the two RCTs which reported the risk of death in a sub group of traumatic subarachnoid haemorrhage patients, the pooled odds ratio was 0.59 (95% CI 0.37 to 0.94). Three RCTs reported death and severe disability as an outcome in this subgroup, and the pooled odds ratio was 0.67 (95% CI 0.46 to 0.98). REVIEWER'S CONCLUSIONS: This systematic review of randomized controlled trials of calcium channel blockers in acute traumatic head injury patients shows that considerable uncertainty remains over their effects. The effect of nimodipine in a subgroup of brain injury patients with subarachnoid haemorrhage shows a beneficial effect, though the increase in adverse reactions suffered by the intervention group may mean that the drug is harmful for some patients.

Brain Injuries↗

Functional outcomes following anoxic brain injury: a comparison with traumatic brain injury.

PRIMARY OBJECTIVE: To compare the functional outcomes of patients with anoxic brain injury (ABI) and patients with traumatic brain injury (TBI) following inpatient rehabilitation. RESEARCH DESIGN: Retrospective chart review. METHODS AND PROCEDURES: Data on 68 patients with brain injury (34 with ABI and 34 with TBI) were collected. MAIN OUTCOMES AND RESULTS: The ABI and TBI groups were demographically similar, except that patients with ABI were more likely to be married. Both groups significantly improved their function and were similar upon discharge. For the ABI group, there were trends toward a shorter length of stay, increased total FIM efficiency and decreased cost of stay when compared with the TBI group. The patients with ABI tended to be discharged to a sub-acute rehabilitation facility more than those in the TBI group. CONCLUSIONS: This study is important because it shows that patients with ABI benefit from inpatient rehabilitation and made significant functional gains comparable to the gains of patients with TBI.

Activities of Daily Living↗