Post-injury Interval Research Articles

4-hydroxynonenal, a lipid peroxidation product, rapidly accumulates following traumatic spinal cord injury and inhibits glutamate uptake.

Traumatic injury to the spinal cord initiates a host of pathophysiological events that are secondary to the initial insult. One such event is the accumulation of free radicals that damage lipids, proteins, and nucleic acids. A major reactive product formed following lipid peroxidation is the aldehyde, 4-hydroxynonenal (HNE), which cross-links to side chain amino acids and inhibits the function of several key metabolic enzymes. In the present study, we used immunocytochemical and immunoblotting techniques to examine the accumulation of protein-bound HNE, and synaptosomal preparations to study the effects of spinal cord injury and HNE formation on glutamate uptake. Protein-bound HNE increased in content in the damaged spinal cord at early times following injury (1-24 h) and was found to accumulate in myelinated fibers distant to the site of injury. Immunoblots revealed that protein-bound HNE levels increased dramatically over the same postinjury interval. Glutamate uptake in synaptosomal preparations from injured spinal cords was decreased by 65% at 24 h following injury. Treatment of control spinal cord synaptosomes with HNE was found to decrease significantly, in a dose-dependent fashion, glutamate uptake, an effect that was mimicked by inducers of lipid peroxidation. Taken together, these findings demonstrate that the lipid peroxidation product HNE rapidly accumulates in the spinal cord following injury and that a major consequence of HNE accumulation is a decrease in glutamate uptake, which may potentiate neuronal cell dysfunction and death through excitotoxic mechanisms.

Frontal Lobe Changes after Severe Diffuse Closed Head Injury in Children

In view of the pathophysiology and biomechanics of severe closed head injury (CHI) in children, we postulated that the frontal lobes sustain diffuse injury, even in the absence of focal brain lesions detected by magnetic resonance imaging (MRI). This study quantitated the morphological effects of CHI on the frontal lobes in children who sustained head trauma of varying severity. The MRI findings of 14 children who had sustained severe CHIs (Glasgow Coma Scale score of < or = 8) were compared with the findings in a matched group of 14 children having sustained mild head injuries (Glasgow Coma Scale score of 13-15). The patients ranged in age from 5 to 15 years at the time of their MRIs, which were acquired at least 3 months postinjury. MRI findings revealed no focal areas of abnormal signal in the frontal lobes. Volumetric analysis disclosed that the total prefrontal cerebrospinal fluid increased and the gray matter volume decreased in the patients with severe CHI, relative to the mildly injured comparison group. Gray matter volume was also reduced in the orbitofrontal and dorsolateral regions of the brains of children with severe CHI, relative to the children who sustained mild head trauma. These volumetric findings indicate that prefrontal tissue loss occurs after severe CHI in children, even in the absence of focal brain lesions in this area. Nearly two-thirds of the children who sustained severe CHIs were moderately disabled after an average postinjury interval of 3 years or more, whereas 12 of the 14 patients with mild CHIs attained a good recovery (2 were moderately disabled) by the time of study.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a single administration of fibroblast growth factor on vascular wall reaction to injury

Expansion of the vascular wall through formation of neointimal fibromuscular lesions is the basic mechanism underlying stenosis of vascular grafts, restenosis of arteries treated by balloon angioplasty, and other major cardiovascular problems. This study examined the effect of a single, systemic, low dose of basic fibroblast growth factor (bFGF) on formation of neointimal fibromuscular lesions in response to injury. New Zealand white rabbits (n = 76) were subjected to balloon injury of the abdominal aorta. Forty-five rabbits were given a single intravenous dose of bFGF (0.5 microgram/kg) immediately after injury, and 31 rabbits were given only the vehicle solution as controls. After 2 (n = 15), 5 (n = 21), 14 (n = 29), or 28 (n = 11) days the rabbits were sacrificed. Those rabbits receiving the single administration of bFGF exhibited significantly greater intimal thickening (intima/media ratio) than the control group at 5 days (mean +/- standard error of the mean, 0.091 +/- 0.009 versus 0.058 +/- 0.006; p < 0.002), but not at 14 or 28 days. These results were achieved without any significant differences in mitotic indices, as determined by a mitostatic method, between the two groups at any postinjury interval examined. The findings suggest that a single systemic dose of exogenous bFGF has a relatively long term effect on enhancing the neointimal response to vascular injury. Therefore, local control of endogenous bFGF may be useful in limiting formation of vascular neointimal fibromuscular lesions, thus improving the long-term results of vascular grafts, balloon angioplasty, and other cardiovascular procedures.

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.

Altered patterns of reflex excitability subsequent to contusion injury of the rat spinal cord.

1. The present study investigated regulation of reflex excitability after experimental contusion injury of the spinal cord. 2. Four measures of H-reflex excitability were evaluated in normal rats and at 6, 28, and 60 days after contusion injury at the T8 level: 1) reflex thresholds, 2) slope of the reflex recruitment curves, 3) maximal plantar H-reflex/maximal plantar M-response (Hmax/Mmax) ratios, and 4) rate-sensitive depression (i.e., the decrease in reflex magnitude relative to repetition rate). 3. Tested as a function of the afferent volley magnitude, the thresholds for reflex initiation fell progressively subsequent to contusion injury. No change was observed at 6 days postinjury, and the decrease at 28 days was not significant. However, by 60 days postinjury, the threshold had decreased by 23% of the maximal afferent volley, and this decrease was significant, [analysis of variance (ANOVA, P < or = 0.01)]. 4. Hmax/Mmax ratios elicited in postcontusion animals at 0.3 Hz were not significantly different from those recorded in normal animals. 5. The slopes of the recruitment curves were markedly reduced subsequent to contusion injury. The decrease was greatest at 6 days postinjury. Although some recovery toward normal occurred at 28 and 60 days postinjury, the slopes of recruitment curves in postcontusion animals remained significantly decreased. 6. H-reflexes elicited at 1-5 Hz were less sensitive to rate depression in postcontusion animals than in normal animals at the same respective frequencies. The decrease was progressive in onset, becoming significant by 28 days postinjury, and of an enduring nature, i.e., still significantly different from normal in the reflexes tested 60 days postinjury. 7. Rate sensitivity of the tibial nerve monosynaptic reflex (MSR) was also compared in normal and postcontusion animals. Rate sensitivity of the tibial MSRs was significantly reduced at 28 and 60 days post-contusion, compared with normal animals. 8. These data indicate that significant changes in lumbar reflex excitability result from midthoracic contusion injury of the spinal cord. These changes include reflex threshold, slope of recruitment, and rate-sensitive depression. Although recruitment slope was most altered in the shortest postinjury interval tested, followed by some recovery, the other changes were progressive in onset and enduring in duration.