Accession Number : ADA188067

Title :   Neuropeptides in Experimental Head Injury.

Descriptive Note : Annual rept. 1 Mar 86-28 Feb 87,

Corporate Author : VETERANS ADMINISTRATION MEDICAL CENTER SAN FRANCISCO CA

Personal Author(s) : Faden, Alan I ; McIntosh, Tracy K

PDF Url : ADA188067

Report Date : 28 Feb 1987

Pagination or Media Count : 39

Abstract : Much of the damage resulting from ischemic or traumatic insults to the central nervous system appears to result from secondary injury mechanisms relating to the release of endogenous factors. Endogenous opioids may represent one such class of pathophysiological factors, and have been implicated in traumatic spinal cord injury, ischemic spinal cord injury and ischemic brain injury. The studies covered under the present contract examine the potential pathophysiological role of endogenous opioids and their receptor-mediated changes following traumatic brain injury in both cats and rats. Utilizing a fluid percussion device we have evaluated the effects of graded levels of injury on outcome measures, including mean arterial pressure, intracranial pressure, electroencephalographic (EEG) activity, and cerebral blood flow in the cat. In a continue of studies begun during the first year of the present contract, we have compared the effectiveness of the opiate antagonist WIN44, 441-3, which has enhanced activity at the kappa-opiate receptor, with its inactive stereoisomer WIN44, 441-2, saline, and dopamine hydrochloride. Finally, we have initiated pilot studies utilizing nuclear magnetic resonance spectroscopy (MRS) to evaluate the dynamic in vivo metabolic response to traumatic brain injury in the rat. These studies have shown that transient changes in high energy phosphates and intracellular pH occur in response to traumatic brain injury. This decreased PCr/Pi ratio in the absence of hypoxia or tissue acidosis may be a reflection of mitochondrial dysfunction and may thus be a marker of irreversible tissue injury.

Descriptors :   *PEPTIDES, *TRANSIENTS, *BRAIN DAMAGE, *NEUROCHEMISTRY, ACIDOSIS, BLOOD CIRCULATION, BLOOD PRESSURE, BRAIN, CATS, CELLS(BIOLOGY), CENTRAL NERVOUS SYSTEM, CEREBRUM, DYSFUNCTION, ELECTROENCEPHALOGRAPHY, FLUIDS, HEAD(ANATOMY), HIGH ENERGY, HYPOXIA, INTERNAL, IRREVERSIBLE PROCESSES, MEAN, MITOCHONDRIA, NERVES, NUCLEAR MAGNETIC RESONANCE, NUCLEAR RADIATION SPECTROSCOPY, OPIUM ALKALOIDS, PH FACTOR, PHOSPHATES, PILOT STUDIES, PRESSURE, RATIOS, RATS, REFLECTION, SECONDARY, SKULL, SPINAL COLUMN, SPINAL CORD, TISSUES(BIOLOGY), TRAUMA, WOUNDS AND INJURIES, PATHOPHYSIOLOGY, RESPONSE(BIOLOGY), BLOOD PRESSURE, ISCHEMIA, PHARMACOLOGICAL ANTAGONISTS

Subject Categories : Medicine and Medical Research
      Biochemistry
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE