No abstract

To test the hypothesis that concussive brain injury autoregulation of cerebral blood flow (CBF), 24 cats were subjected to hemorrhagic hypotension in 10-mm Hg increments while measurements were made of arterial and intracranial pressure, CBF, and arterial blood gases. Eight cats served as controls, while eight were subjected to mild fluid percussion injury of the brain (1.5 to 2.2 atmospheres) and eight to severe injury (2.8 to 4.8 atmospheres). Injury produced only transient changes in arterial and intracranial pressure, and no change in resting CBF. Impairment of autoregulation was found in injured animals, more pronounced in the severe-injury group. This could not be explained on the basis of intracranial hypertension, hypoxemia, hypercarbia, or brain damage localized to the area of the blood flow electrodes. It is, therefore, concluded that concussive brain injury produces a generalized loss of autoregulation for at least several hours following injury.

The neuronal response to complete cerebral ischemia (CCI) of 5-15 min duration was evaluated at the light and electron microscopic level subsequent to postischemic recirculation periods of up to 60 min. Following postischemic reperfusion, the homogeneous neuronal changes characteristic of permanent CCI were modified into a heterogeneous pattern of selectively vulnerable neuronal responses. Four basic types of neuronal injury were represented within this heterogeneous neuronal population. The Type I neuronal response was most numerous and consisted of chromatin clumping, nucleolar condensation and a breakdown of polysomes. This response may represent a reversal of some of the neuronal changes observed after permanent CCI. In addition to the above changes, Type II neurons contained swollen mitochondria and Golgi saccules which appeared as microvacuoles under the light microscope. Type III neurons displayed varying degrees of neuronal shrinkage and numerous swollen mitochondria. Type IV neurons were markedly shrunken and electron-dense with few identifiable subcellular structures. The distribution of Type I neurons was random but the other neuronal responses occurred in "selectively vulnerable" brain regions. The number of Type II, III, and IV neurons increased with extended insult durations but were unaffected by the length of recirculation. Ten minutes of CCI represented the threshold for a significant increase in the number of severely altered neurons. These findings suggest that considerable neuronal injury may be present after 10-15 min of CCI, and the lack of a recirculation period following CCI appears to afford the brain parenchyma an extensive degree of structural protection.

Fasted Wistar rats were given a mild level of traumatic brain injury (TBI) and then subjected to 6 min of transient forebrain ischemia 24 h posttrauma. One group was given simultaneous 1 mg/kg scopolamine and 4 mg/kg phencyclidine intraperitoneally (IP) 15 min before trauma and another group an equal volume of plasmalyte A solution. After 7 days of postinjury survival, placebo-treated rats demonstrated increased posttraumatic vulnerability to secondary ischemic CA1 neuronal death even 24 h after trauma. This finding confirmed that increased posttraumatic ischemic vulnerability persists for at least 24 h even following mild trauma. Combined muscarinic receptor and N-methyl-D-aspartate (NMDA) receptor coupled ion channel blockade given and present during the mild TBI statistically attenuated this enhanced secondary ischemic CA1 neuronal death and thus posttraumatic increased ischemic vulnerability. Placebo-treated rats had 335.3 +/- 93.6 CA1 neurons/10(6) microns 2 and drug-treated rats had 844.8 +/- 184.9 CA1 neurons/10(6) microns 2. This result suggests that muscarinic and/or NMDA receptor-mediated events confined to TBI and the early posttraumatic period are in part responsible for the phenomenon of increased posttraumatic ischemic vulnerability.