Effects of traumatic brain injury on regional cerebral blood flow in rats as measured with radiolabeled microspheres.

To clarify the effect of experimental brain injury on regional CBF (rCBF), repeated rCBF measurements were performed using radiolabeled microspheres in rats subjected to fluid-percussion traumatic brain injury. Three consecutive microsphere injections in six uninjured control rats substantiated that the procedure induces no significant changes in hemodynamic variables or rCBF. Animals were subjected to left parietal fluid-percussion brain injury of moderate severity (2.

Cholesterol modifies the short-range repulsive interactions between phosphatidylcholine membranes.

Pressure versus distance relationships have been obtained for egg phosphatidylcholine bilayers containing a range of cholesterol concentrations. Water was removed from between adjacent bilayers by the application of osmotic pressures in the range of 0.4-2600 atm (4 x 10(5)-2.

Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model.

Experimental fluid-percussion models produce brain injury by rapidly injecting saline into the closed cranium. In the present study we characterize the physiological, histopathological and neurological responses to mechanical brain injury in the rat produced by lateral fluid-percussion injury of graded severity. Physiological experiments (n = 105) demonstrated that all levels of injury produced an acute and transient systemic hypertension and bradycardia.

Effects of the N-methyl-D-aspartate receptor blocker MK-801 on neurologic function after experimental brain injury.

Pharmacologic inhibition of excitatory amino acid (EAA) neurotransmission attenuates cell death in models of global and focal ischemia and hypoglycemia and improves neurologic outcome after experimental traumatic spinal cord injury. The present study examined the effects of the noncompetitive N-methyl-D-aspartate (NMDA) receptor blocker MK-801 on cardiovascular and neurologic function after experimental fluid-percussion (FP) brain injury in the rat. Animals received either an intravenous bolus of MK-801 (1 mg/kg) or saline (equal volume) 15 min prior to FP brain injury or 15 min following FP brain injury.

Thyrotropin-releasing hormone and central nervous system trauma.

TRH and TRH analogues improve physiological function, survival, and neurological outcome in a variety of models of CNS trauma, including impact spinal cord injury in cats and rats, fluid-percussion-induced brain injury in rats, and compression-induced brain injury in cats. The mechanism by which TRH improves such functions may relate to its ability to improve blood flow and metabolism in the region of injury. Beneficial effects on blood flow may possibly relate to antagonism of the physiological effects of endogenous opioids, leukotrienes, or platelet-activating factor.

Studies of the ethanol-induced interdigitated gel phase in phosphatidylcholines using the fluorophore 1,6-diphenyl-1,3,5-hexatriene.

It is now well established that a number of amphiphilic molecules such as ethanol can induce the formation of the fully interdigitated gel phase in phosphatidylcholines. We have shown earlier that alcohols such as ethanol induce biphasic melting behavior in phosphatidylcholines [Rowe, E. S.

Levels of endogenous opioids and effects of an opiate antagonist during regional cerebral ischemia in rats.

Changes in endogenous opioid concentrations and the effect of treatment with the opiate receptor antagonist WIN 44,441-3 (WIN) were evaluated after middle cerebral artery occlusion (MCA-O) in rats. Animals treated with WIN at doses of 0.4 to 400 micrograms/kg 15 min, 3 hr and 6 hr after MCA-O had significantly higher mean arterial blood pressure than saline controls (P less than .

Selective sparing of NADPH-diaphorase neurons in neonatal hypoxia-ischemia.

Excitatory amino acids have been implicated in ischemic neuronal injury. To test this hypothesis in neonatal hypoxia-ischemia, lesions of the cortex and striatum were induced in 7-day-old rats by unilaterally ligating their carotid arteries and subjecting them to hypoxic conditions for 2 hours. Brains examined 1 week later demonstrated, within the regions of ischemic damage, a striking preservation of neurons that stained histochemically for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity.

Treatment with the thyrotropin-releasing hormone analog CG3703 restores magnesium homeostasis following traumatic brain injury in rats.

Treatment with thyrotropin-releasing hormone (TRH) analogs following traumatic injury to the central nervous system (CNS) improves neurological outcome through mechanisms that remain unclear. Previous studies have shown that traumatic brain injury is associated with a profound decline in intracellular free magnesium (Mgf) and in total tissue magnesium (Mgt), the extent of Mgf decline being linearly correlated to the severity of injury and resultant neurological deficit. We have used 31P magnetic resonance spectroscopy and atomic absorption spectrophotometry, respectively, to measure cerebral Mgf concentration and Mgf content in rats following fluid percussion brain trauma and treatment with the TRH analog, CG3703.

Thermomechanical and transition properties of dimyristoylphosphatidylcholine/cholesterol bilayers.

Mixtures of dimyristoylphosphatidylcholine (DMPC) and cholesterol (Chol) have been used to examine the effects of cholesterol on the chain crystallization transitions and thermomechanical properties in phospholipid bilayer membranes. The mechanical properties--elastic moduli and level of tension at membrane rupture--were derived from micropipet pressurization of giant single-walled vesicles. Also, the micropipet method allowed temperature-dependent area transitions to be measured at constant membrane tension.

An epidural intracranial pressure monitor for experimental use in the rat.

We described the construction and use of a simple and reliable catheter system that can be used to monitor intracranial pressure (ICP) from the epidural space in rats in an experimental setting. The catheter system is easily fabricated in the laboratory from readily available materials. The monitor is fitted flush with the inner table through a burr hole in the temporal squama.

Nonedited 1H NMR lactate/n-acetyl aspartate ratios and the in vivo determination of lactate concentration in brain.

The 1H lactate/n-acetyl aspartate ratio is commonly used for the quantitation of brain lactate under pathological conditions. We demonstrate that the intensity of the lactate methyl region in water-suppressed, nonedited 1H spectra increases following mild brain trauma as a result of factors other than lactate accumulation.

An analogue of thyrotropin-releasing hormone improves outcome after brain injury: 31P-NMR studies.

The effects of a long-acting, centrally active thyrotropin-releasing hormone (TRH) analogue, CG3703, on neurological outcome, survival, and intracellular metabolism were evaluated after experimental fluid-percussion (FP) brain injury (2.0-2.4 atm) in the rat.

Treatment of left-sided ulcerative colitis with 4-aminosalicylic acid enemas. A double-blind, placebo-controlled trial.

Twenty-five patients with active left-sided ulcerative colitis were randomly assigned to receive either 2 g of 4-aminosalicylic acid (para-aminosalicylic acid) or placebo in a 60-mL volume as a nightly retention enema. The duration of treatment was 8 weeks. Disease activity was assessed by grading clinical symptoms of blood, mucus, urgency, sigmoidoscopic findings, and degree of histologic inflammation in rectal biopsies.

Decline in intracellular free Mg2+ is associated with irreversible tissue injury after brain trauma.

Much of the tissue damage resulting from trauma to the central nervous system appears to result from secondary, delayed biochemical changes that follow primary mechanical injury. However, the early biochemical events remain to be elucidated. In the present studies, we have used phosphorus (31P) magnetic resonance spectroscopy (MRS) to examine in vivo, the temporal changes in brain intracellular free Mg2+ concentration following fluid percussion head injury in rats.

31P NMR characterization of graded traumatic brain injury in rats.

Irreversible tissue injury following central nervous system trauma is believed to result from both mechanical disruption at the time of primary insult, and more delayed "autodestructive" processes. These delayed events are associated with various biochemical changes, including alterations in phosphate energy metabolism and intracellular pH. Using 31P NMR, we have monitored the changes in phosphorus energy metabolism and intracellular pH in a single hemisphere of the rat brain over an 8-h period following graded, traumatic, fluid percussion-induced brain injury.

Changes in cellular bioenergetic state following graded traumatic brain injury in rats: determination by phosphorus 31 magnetic resonance spectroscopy.

Phosphorus 31 magnetic resonance spectroscopy (31P MRS) was used to study noninvasively the intracellular free Mg2+ concentration and cellular bioenergetic state of rat brain in vivo before and after fluid percussion-induced traumatic brain injury of graded severity. Brain injury was induced at four levels: low (1.0 +/- 0.

Magnesium deficiency exacerbates and pretreatment improves outcome following traumatic brain injury in rats: 31P magnetic resonance spectroscopy and behavioral studies.

The biochemical mechanisms mediating delayed or secondary tissue injury after central nervous system trauma remain speculative. We have demonstrated previously that traumatic brain injury in rats causes a rapid decline in tissue intracellular free magnesium [Mg]f and total magnesium [Mg]t concentrations, which were significantly correlated with injury severity. In order to examine the relationship between magnesium and traumatic brain injury, we assessed whether (1) magnesium deficiency exacerbates or (2) magnesium treatment improves posttraumatic outcome following fluid-percussion brain injury (2.

Traumatic brain injury in the rat: effects on lipid metabolism, tissue magnesium, and water content.

Tissue levels of free fatty acids (FFA), total phospholipid, cholesterol, thromboxane B2, water, Na+, K+, and Mg2+ were measured in rat brain after lateral fluid-percussion brain injury of moderate severity (2.0-2.2 atm).

Decrease in total and free magnesium concentration following traumatic brain injury in rats.

31P magnetic resonance spectroscopy was used to determine the intracellular free Mg2+ concentration prior to and following fluid percussion induced traumatic brain injury in rats. Prior to injury, cerebral intracellular free Mg2+ concentration in the rat was 0.93 +/- 0.

Tris buffer causes acyl chain interdigitation in phosphatidylglycerol.

The structure of the gel phase and the properties of the acyl chain disordering transition of dipalmitoyl phosphatidylglycerol (DPPG) have been studied using differential scanning calorimetry, differential scanning dilatometry, and X-ray diffraction. In the presence of small, monovalent cations, DPPG at 22 degrees C exists in a lamellar phase in which the hydrocarbon chains are tilted from the perpendicular to the bilayer surface. Around 34 degrees C, there is a small pretransition (delta H less than 1 kcal/mol) followed by the main transition at 40.

Steric repulsion between phosphatidylcholine bilayers.

The change in pressure needed to bring egg phosphatidylcholine bilayers into contact from their equilibrium separation in excess water has been determined as a function of both distance between the bilayers and water content. A distinct upward break in the pressure-distance relation appears at an interbilayer separation of about 5 A, whereas no such deviation is present in the pressure-water content relation. Thus, this break is not a property of the dehydration process per se, but instead is attributed to steric repulsion between the mobile lipid head groups that extend 2-3 A into the fluid space between bilayers.

Alterations in regional concentrations of endogenous opioids following traumatic brain injury in the cat.

Delayed injury following trauma to the central nervous system (CNS) may be due to the release or activation of endogenous factors. Endogenous opioid peptides have been proposed as one such class of injury factors, based on pharmacological studies demonstrating a therapeutic effect of naloxone and other opiate receptor antagonists following CNS injury. However, changes in brain opioid concentrations following injury have not been evaluated.