Neurobehavioral functional deficits following closed head injury in the neonatal pig.

Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Experimental Neurology (Impact Factor: 4.62). 04/2007; 204(1):234-43. DOI: 10.1016/j.expneurol.2006.10.010
Source: PubMed

ABSTRACT Neurobehavioral deficits in higher cortical systems have not been described previously in a large animal model of diffuse brain injury. Anesthetized 3-5 day old piglets were subjected to either mild (142 rad/s) or moderate (188 rad/s) rapid non-impact axial rotations of the head. Multiple domains of cortical function were evaluated 5 times during the 12 day post-injury period using tests of neurobehavioral function devised for piglets. There were no observed differences in neurobehavioral outcomes between mild injury pigs (N=8) and instrumented shams (N=4). Moderately injured piglets (N=7) had significantly lower interest in exploring their environment and had higher failure rates in visual-based problem solving compared to instrumented shams (N=5) on days 1 and 4 after injury. Neurobehavioral functional deficits correlated with neuropathologic damage in the neonatal pigs after inertial head injury. Injured axons detected by immunohistochemistry (beta-APP) were absent in mild injury and sham piglets, but were observed in moderately injured piglet brains. In summary, we have developed a quantitative battery of neurobehavioral functional assessments for large animals that correlate with neuropathologic axonal damage and may have wide applications in the fields of cardiac resuscitation, stroke, and hypoxic-ischemic brain injury.

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    Seminars in Neurology 02/2015; 35(1):20-28. DOI:10.1055/s-0035-1545080 · 1.78 Impact Factor
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    ABSTRACT: Introduction: Modification of cerebral perfusion pressure and cerebral blood flow are crucial components of the therapies designed to reduce secondary damage after traumatic brain injury (TBI). Previously we documented a robust decrease in cerebral blood flow (CBF) after rapid sagittal head rotation in our well-validated animal model of diffuse TBI. Mechanisms responsible for this immediate (<10 min) and sustained (~24 hours) reduction in CBF have not been explored. Hypothesis: Because the carotid arteries are a major source of cerebral blood flow, we hypothesized that blood flow through the carotid arteries (Q) and vessel diameter (D) would decrease following rapid non-impact head rotation without cervical spine injury. Methods: Four-week old (toddler) female piglets underwent rapid (<20msec) sagittal head rotation without impact, previously shown to produce diffuse TBI with reductions in CBF. Ultrasound images of the bilateral carotid arteries were recorded at baseline (pre-injury), as well as immediately after head rotation and 15, 30, 45, and 60 minutes after injury. Diameter (D) and waveform velocity (V) were used to calculate blood flow (Q) through the carotid arteries using the equation Q = (0.25)πD2V. D, V, and Q were normalized to the pre-injury baseline values to obtain a relative change after injury in right and left carotid arteries. Three-way ANOVAs and post-hoc Tukey-Kramer analyses were used to assess statistical significance of injury, time, and side. Results: The relative change in carotid artery diameter and flow was significantly decreased in injured animals in comparison to uninjured sham controls (p<0.0001 and p=0.0093, respectively) and did not vary with side (p > 0.39). The average carotid blood velocity did not differ between sham and injured animals (p=0.91). Conclusion: These data suggest that a reduction in global CBF after rapid sagittal head rotation may be partially mediated by a reduction in carotid artery flow, via vasoconstriction.
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