Journal of neurotrauma
-
Journal of neurotrauma · Jul 2002
Traumatic axonal injury after closed head injury in the neonatal pig.
Closed head injury is the leading cause of morbidity and mortality in infants and children, and results in pathologies such as diffuse axonal injury (DAI) and subarachnoid hematoma (SAH). To better understand the mechanical environment associated with closed head injury in the pediatric population, animal models that include salient features of human infant brain must be utilized. Based on detailed information regarding the parallels between brain development in the pig and the human, the 3-5-day-old piglet was used to represent the infant at less than 3 months of age. ⋯ Mapping of the regional pattern of TAI revealed injured axons predominantly in central and peripheral white matter tracts in the frontal and temporal lobes and in the midbrain. The number of injured axons was equivalent in both hemispheres, and did not correlate to the load applied to the head. Together, these data demonstrate that rapid rotation of the piglet head without impact results in SAH and TAI, similar to that observed in children following severe brain trauma.
-
Journal of neurotrauma · Jul 2002
Comparative StudySystemic administration of a calpain inhibitor reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhage in the rat.
Increases in intracellular calcium and subsequent activation of calcium-activated proteases (e.g., calpains) may play a critical role in central nervous system injury. Several studies have implicated calpain activation following subarachnoid hemorrhage (SAH). This study evaluated the effect of a calpain inhibitor administration following SAH in the rat on behavioral deficits (postinjury days 1-5, employing a battery of well-characterized assessment tasks), and blood-brain barrier permeability changes (48 h post-SAH, quantifying the microvascular alterations according to the extravasation of protein-bound Evans Blue using a spectrophotofluorimetric technique). ⋯ Results indicated that Calpain Inhibitor II treatment after SAH significantly improved (a) beam balance time (day 1, p < 0.05), but not beam balance score, (b) latency to traverse the beam on days 1-4 (day 1-3, p < 0.001; day 4, p < 0.01), and (c) loss in body weight on days 4-5 (p < 0.05). Evans Blue dye extravasation was significantly less in SAH Calpain Inhibitor II-treated rats compared to SAH vehicle-treated rats in seven out of the eight brain regions studied (p < 0.001, 0.01, and 0.05). These results suggest that pharmacological inhibition of a relatively selective, membrane-permeant calpain inhibitor can significantly reduce some pathophysiological SAH consequences, and indicate that the inhibition of calpain may be a beneficial therapeutic approach to reduce post-SAH global brain dysfunction.
-
Journal of neurotrauma · Jun 2002
Effects of mild hypothermia and alkalizing agents on brain injuries in rats with acute subdural hematomas.
Brain ischemia is the leading pathopysiological mechanism in the development of secondary brain damage after acute subdural hematoma (SDH). Hypothermia has been employed as an effective cerebroprotective treatment on brain injuries, but the control of the general condition is very difficult under hypothermia, and various severe complications have been reported. Cerebral acidosis in the ischemic area is one of the important factors augmenting the brain edema formation. ⋯ Furthermore, the volume of infarction at 24 h after the hematoma induction (54 +/- 3 mm(3); p < 0.01) was significantly smaller by the combined treatment compared with normothermia (70 +/- 2 mm(3)). The present findings indicate that mild hypothermia of 35 degrees C combined with THAM presents a potent cerebroprotective strategy. The protection of the BBB is one of the possible cerebroprotective mechanisms in this rat acute SDH model.
-
Journal of neurotrauma · May 2002
Comparative StudyThe importance of brain temperature in patients after severe head injury: relationship to intracranial pressure, cerebral perfusion pressure, cerebral blood flow, and outcome.
Brain temperature was continuously measured in 58 patients after severe head injury and compared to rectal temperature, intracranial pressure, cerebral blood flow, and outcome after 3 months. The temperature difference between brain and rectal temperature was also calculated. Mild hypothermia (34-36 degrees C) was also used to treat uncontrollable intracranial pressure (ICP) above 20 mm Hg when other methods failed. ⋯ The lowest CBF was measured in patients with a brain temperature <36.0 degrees C and a negative brain-rectal temperature difference (17.1 +/- 14.0 mL/100 g/min). A positive trend for improved outcome was seen in patients with mild hypothermia. Simultaneous monitoring of brain and rectal temperature provides important diagnostic and prognostic information to guide the treatment of patients after severe head injury (SHI) and the wide differentials that can develop between the brain and core temperature, especially during rapid cooling, strongly supports the use of brain temperature measurement if therapeutic hypothermia is considered for head injury care.
-
Journal of neurotrauma · May 2002
Caspase-3-mediated cleavage of amyloid precursor protein and formation of amyloid Beta peptide in traumatic axonal injury.
Immunohistochemical studies demonstrate accumulation of the beta-amyloid precursor protein (APP) within injured axons following traumatic brain injury (TBI). Despite such descriptions, little is known about the ultimate fate of accumulating APP at sites of traumatic axonal injury (TAI). Recently, caspase-3-mediated cleavage of APP and subsequent Abeta deposition was linked to apoptotic neuronal death pathways in hippocampal neurons following ischemic and excitotoxic brain injury. ⋯ Further, CMAP was colocalized with Abeta formation in foci of TAI. The current study demonstrates that caspase-3 cleavage of APP occurs in TAI and is associated with formation of Abeta peptide. These findings are of interest given recent epidemiological studies supporting an association between TBI and later risk for AD development.