Cortical Specific Gravity Research Articles

Recirculation after cerebral ischemia. Simultaneous measurement of cerebral bloodflow, brain edema, cerebrovascular permeability and cortical EEG in the rat.

The 4-vessel occlusion rat model of cerebral ischemia was modified to permit the simultaneous measurement of cerebral blood flow (hydrogen clearance), brain edema (specific gravity), cerebrovascular permeability (14C-AIB) and electrocardiogram. Surgery was performed in one stage in the anesthetised, paralysed and ventilated rat and severe hemispheric ischemia was produced in all animals. Electrode implantation did not alter cortical specific gravity or Ki for 14C-AIB. During 4-vessel occlusion mean cortical CBF was 5.8 +/- 1.4 ml-1 100 g-1 min. and this was associated with an isoelectric ECoG; 15 min of ischemia produced a significant reduction in mean cortical specific gravity (increase in brain edema). Following 15 min ischemia, 180 min of recirculation were permitted. Post-ischemic blood flow showed an immediate hyperemia (CBF = 202 +/- 12 ml-1 100 g-1 min.) followed by hypoperfusion (CBF = 58 +/- 8 ml-1 100 g-1 min). There was an early further decrease in cortical specific gravity. Further recirculation led to a significant increase in cortical specific gravity (resolution of brain edema). The transfer constant (Ki) for 14C-AIB was not altered at any stage in recirculation. This appears to be a model of pure cytotoxic edema until 180 min recirculation after 15 min cerebral ischemia. Recirculation permitted return of cortical electrical activity.

Nω-nitro-L-arginine attenuates early ischemic neuronal damage of prolonged focal cerebral ischemia and recirculation in rats

The present study aimed to .examine the effects of NCJ)-nitro-L-arginine (LNA) on the early ischemic neuronal damage (EIND). All the experiments were carried out under general anesthesia, maintaining the blood gases and the body temperature within the physiologica.l ranges. The local CBF, the topographically corresponding cortical specific gravity, and the volume of fiNO were determined in each rat, which was subjected to prolonged or temporary occlusion of middle cerebral artery (MCA) using our original miniclip. Significant cortical edema developed only in the brain area where the loca.f CBF valUe was below 200 ml 100 g-l min-1 The prolonged MCA occlusion for 1, 2, and 4 h induced a time-dependent increase in the severity of cortical edema and the volume of fiNO. Removal of the clip invariably induced recirculation. Compared to that induced by 4 h prolonged ischemia, the brain damage was improved by 1 h MeA occlusion followed by 3 h recirculation, whereas it was significantly worsened by 2 h ischemia followed by 2 h recirculation. While LNA [1 mgt i.p., given two times during the experiment] only partially1nhibited -the activity of brain nitric oxide synthase, it remarkably ameliorated fiNO of both prolonged ischemia and recirculation in this model. The above findings indicate the pathogenic role of nitric oxide in prolonged ischemia as well as recirculation. [Neural Res 1997; 19: 192–203].

Effect of hypothermia, dichloroacetate, and deferoxamine in the treatment for cortical edema and functional recovery after experimental cortical impact in the rat.

To investigate the effects of hypothermia alone or in combination with dichloroacetic acid (DCA) and/or deferoxamine (DFO) in reducing cortical edema (CE) and improving neurologic functional recovery after moderate closed and head trauma with controlled cortical impact (CCI). Anesthetized rats were randomized to receive right parietal moderate CCI (impact depth 2 mm, speed 3.5 m/sec) or sham operations. Immediately after trauma, the animals underwent selective brain cooling to 30 degrees C (temporalis muscle temperatures). Ten minutes after trauma, the randomized animals received intraperitoneal doses of DCA (25 mg/kg), DFO (50 mg/kg), both DCA and DFO, or equivolume normal saline. For evaluation of cortical edema, some animals (n = 42) were sacrificed 4 hours after trauma and cortical specific gravity (SpG) was determined gravimetrically. The other animals (n = 47) were evaluated for functional recovery beginning 6 days posttrauma. Neurobehavioral performance was assessed in the Morris water maze. Cortical edema was significantly less in the animals treated with hypothermia (SpG = 1.041 +/- 0.001, p < 0.05) compared with the untreated traumatized animals (SpG = 1.037 +/- 0.001). Combination treatment with hypothermia and drug treatment did not reduce cortical edema when compared with no treatment. Hypothermia with and without drug treatment did not improve neurobehavioral performance when compared with no treatment. In this pilot study with a relatively small sample size, hypothermia alone significantly reduced post-CCI cortical edema as measured by SpG. Hypothermia combined with drug treatment did not reduce posttraumatic cortical edema. Hypothermia with and without drug therapy did not improve functional neurologic recovery in the rats subjected to CCI.

BRAIN EDEMA FORMATION AFTER BRAIN INJURY, SHOCK, AND RESUSCITATION

Recent work suggests that increased intracranial pressure (ICP) following brain injury and shock is related to increased central venous pressure (CVP) following resuscitation. To analyze the relationship of intravascular pressures to edema formation and ICP in an experimental model. In a porcine model of cryogenic brain injury and hemorrhagic shock, we studied CVP, mean arterial pressure (MAP), ICP, and cortical water content (CWC, as cortical specific gravity) at baseline (BL), 45 minutes after shock (H45), and 1, 3, 6, 12, and 24 hours (H) after resuscitation. Group 1 was the control group, group 2 brain injury only, group 3 shock only, and group 4 brain injury and shock. Brain injury significantly increased ICP and CWC. Mean arterial pressure significantly correlated with ICP (r = 0.54, p = 0.02) and with CWC (r = -0.48, p = 0.03) in group 4 at 24H but not in the other groups at any time period. There was no significant correlation between CVP and ICP or CWC in any group at any time interval. These data suggest that brain edema formation in the injured hemisphere is related to MAP and not CVP, but variability in MAP accounts for only 29% of the variability in CWC and ICP, suggesting the importance of factors other than hydrostatic pressure in determining the amount of edema and the ICP after brain injury. Previous work demonstrating the significant correlation of polymorphonuclear leukocyte infiltration with ICP (r = 0.71, p < 0.001) and with CWC (r = -0.63, p < 0.001) suggests that inflammation may be one of these factors.

Species differences in cerebral taurine concentrations correlate with brain water content

The notion that taurine (Tau) has an osmoregulatory function in the mammalian brain has not been established, although it has been reported that the severity of hyponatremic edema is proportional to cerebral [Tau]. Tau pools are not easily altered in vivo, but the fact that there are large differences in cerebral taurine levels between mice, rats and guinea pigs offers an opportunity to determine whether endogenous Tau affects volume regulation of the brain in hyposmolal conditions. This issue was investigated by injecting saline or distilled water intraperitoneally at 150 ml/kg in anesthetized mice, rats and guinea pigs. The animals were decapitated 4 h later, and blood osmolality, cortical specific gravity, Na +, K + and amino acid concentrations were determined. In controls, blood osmolality and specific gravity of the cortex were highest in the mouse (304 ± 3mmol/kg; 1.0488 ± 0.0003kg/l), followed by the rat (294 ± 1; 1.0462 ± 0.0002) and the guinea pig (285 ± 2; 1.0445 ± 0.0002). There was a correlation between these measures and cortical Tau levels which were 10.31 ± 0.36mmol/kg in mouse cortex, 6.31 ± 0.18 in rat cortex and 1.37 ± 0.06 in guinea pig cortex. Despite these differences, water-induced cerebrocortical swelling did not differ between the species studied. Interspecies variation in cortical osmolality did not relate to [Na +] and [K +], since the levels of these electrolytes were higher in the guinea pig cortex than in the rat and mouse cortex. After administration of water, the levels of Na + and K + were reduced in rat and guinea pig cortex, while only [Na +] was significantly decreased in mouse cortex. The absence of any differences in swelling of mouse and rat cortex, in spite of a two-fold greater reduction in [Na +] and [K +] in the latter, indicates that the mouse is more dependent on organic osmolytes in volume regulation during acute hyposmolality. This suggestion is supported by the finding that there was a net decrease in amino acids in the mouse cortex, but not in the rat cortex. While the results do not provide any evidence for a role of Tau in acute brain edema, they show, for the first time, a close association between brain water and Tau content.

A rodent model of infusion brain edema: Methodology and pathophysiological effects of saline and protein infusions

To evaluate the potency of putative secondary mediators of brain edema and their possible contribution to edema related brain dysfunction an infusion model of brain edema was developed in rats. 100 ul of fluid (saline, 20% nonautologous protein) was infused over one hour into the left forebrain white matter through a stereotaxically placed (+1.2 mm ant to bregma, 3 mm lateral and 2.9 mm depth) 25 G needle. Brain tissue hydraulic resistance (Rt), regional cerebral blood flow (rCBF), cortical somatosensory evoked potentials (SEPs) and intracranial pressure (ICP) (intraventricular needle) were monitored during the infusion and rCBF CO2 reactivity (hydrogen clearance), local brain water content (microgravimetry), BBB integrity (Evans Blue 2%) and brain histology (H & E. Solochrome-cyanin) were evaluated after the infusion. Saline infusates caused no physiological dysfunction despite ipsilateral expansion and vacuolation of the subcortical white matter, separation of axonal bundles and a significant decrease (p = 3.8 x 10(-5] in local subcortical tissue specific gravity. Cortical histology and specific gravity adjacent to the infusion locus were normal. Rt significantly decreased (p = 6.5 x 10(-4] during the infusion but there were only minor increases in ICP. Findings with 20% protein infusates were similar despite a focal 65% decrement in the rCBF CO2 reactivity adjacent to the infusion site. This study has shown that a simple and inexpensive model of infusion brain edema can be created in the rat and that it provides a useful model for assessing the physiological effects of mediator compounds in the infusate. Potential applications and methodological improvements for this model are discussed.

Effect of enhanced capillary activity on the blood-brain barrier during focal cerebral ischemia in cats.

We hypothesize that enhanced activity of capillary Na,K-ATPase promotes Na+ influx into the brain and causes early edema formation in focal cerebral ischemia. The pharmacologic suppression of brain capillary Na,K-ATPase as a means to ameliorate edema formation was examined using the middle cerebral artery occlusion model in 36 cats. With the help of a catheter inserted into the middle cerebral artery, the ischemic brain area was directly perfused with 10(-5) M ouabain. Perfusion was maintained as intermittent 15-second pulse injections given every 5 (n = 6) or 2 (n = 6) minutes. By this method, the naturally occurring circulatory conditions during ischemia were not altered. Four hours after ischemia, the cortical specific gravity at each of six locations over the ischemic area was compared with the corresponding ischemic blood flow measured by the H2 clearance technique. The results show that ouabain perfused every 2 minutes significantly ameliorated edema formation compared with six control cats perfused with Krebs-Ringer solution. In a separate series of experiments, the Na+ flux across the blood-brain barrier was studied by injecting 22NaCl together with an intravascular reference (cobalt-57-labeled microspheres 15 microns in diameter) into the ischemic area. The brain uptake index of 22Na was markedly increased in the ischemic cortex of six control cats; ouabain treatment in six cats suppressed the increase of Na+ influx. The results support our hypothesis that brain capillary Na,K-ATPase activity increases during early focal ischemia, leading to enhanced Na+ together with H2O flux across the blood-brain barrier.

Effect of indomethacin and a free radical scavenger on cerebral blood flow and edema after cerebral artery occlusion in cats.

Using the middle cerebral artery occlusion model in cats, we evaluated the possible role of the cyclooxygenase pathway in alterations of local cerebral blood flow and the development of cortical edema following prolonged ischemia or recirculation. We divided 57 cats into three groups, and each cat received saline (control), indomethacin, or the free radical scavenger ONO-3144. Each group was subdivided into prolonged ischemia (4 hours of occlusion: PI) and recirculation (2 hours of occlusion followed by 2 hours of recirculation: RC) subgroups. We compared local cerebral blood flow and cortical specific gravity between the PI and RC subgroups of the control and drug-treated groups. In the PI subgroup, indomethacin did not influence the time course of local cerebral blood flow but significantly worsened the decrease in cortical specific gravity. On the other hand, indomethacin significantly improved postischemic hypoperfusion and ameliorated the decrease in cortical specific gravity in the RC subgroup. The effects of ONO-3144 were similar to those of indomethacin, except that ONO-3144 did not affect cortical specific gravity in the PI subgroup. Indomethacin inhibits cyclooxygenase activity, whereas ONO-3144 scavenges the oxygen-centered radical released in the conversion of prostaglandin G2 to prostaglandin H2. Thus, prostaglandins do not seem to play a major role in the occurrence of brain edema due to prolonged regional ischemia. By contrast, oxygen-centered radicals released from the cyclooxygenase pathway appear to be at least partially responsible for the occurrence of recirculation-induced edema and postischemic hypoperfusion.

Effect of a hypertonic lactated Ringer's solution on intracranial pressure and cerebral water content in a model of traumatic brain injury.

There has recently been an increased interest in the use of hypertonic solutions for fluid resuscitation of trauma victims. In this study, we examined the acute cerebral effects of a hypertonic lactated Ringer's solution (measured osmolality = 469 mOsm/kg) in an animal model of traumatic brain injury. Following the production of a cerebral cryogenic lesion, eight New Zealand white rabbits were randomized to undergo hemodilution with either lactated Ringer's (measured osmolality = 254 mOsm/kg) or hypertonic lactated Ringer's. Over the course of the experiment the lactated Ringer's group required significantly more fluid than the hypertonic group to maintain stable central venous and mean arterial pressure (245 +/- 5 ml vs. 132 +/- 20 ml; p less than 0.0001). Osmolality increased in the hypertonic group by 13.5 +/- 3.3 mOsm/kg whereas it decreased in the lactated Ringer's group by 5.5 +/- 2.6 mOsm/kg. Intracranial pressure increased in both groups over the course of the experiment but the increase in pressure was greater in the lactated Ringer's group than the hypertonic group (9.5 +/- 2.4 mm Hg vs. 1.7 +/- 1.5 mm Hg; p less than 0.001). Brain water content was significantly increased in the region of the lesion as assayed by both the wet/dry weight method and cortical specific gravity determinations, but there was no difference between the two treatment groups. Water content of the nonlesioned hemisphere was significantly less in the hypertonic group. This study suggests that hypertonic saline solutions may be useful for the resuscitation of hypovolemic patients with localized brain injury.

Acute effect of angiographic contrast medium on cortical specific gravity after middle cerebral artery occlusion in rats.

Early angiography after cerebral arterial occlusion has been cited as potentially detrimental. This investigation evaluates the effect of acute angiographic contrast medium administration on the cortical edema induced by middle cerebral artery (MCA) occlusion. Sixteen rats underwent MCA occlusion, and after 1 hour half the rats underwent ipsilateral internal carotid injection of meglumine diatrizoate, whereas the remainder underwent cervical internal carotid exposure only. Six rats had only sham operations on the MCA and internal carotid, and 4 other rats served as normal controls. Cortical specific gravity was measured to reflect cerebral edema 4 hours after occlusion or sham operation. Specific gravity of the lateral frontal cortex in the hemisphere ipsilateral to occlusion was 1.0396 +/- 0.0011 (mean +/- SEM) when no angiographic contrast medium was administered, significantly less (p less than 0.01) than in rats exposed to contrast medium (specific gravity 1.0442 +/- 0.0005). The latter value was not significantly different from normal. Other cortical areas on the side of the contrast medium injection were also relatively dehydrated compared with normal controls. Early meglumine diatrizoate administration after MCA occlusion results in a decrease in cerebral cortical edema, possible by inducing an osmotic gradient that draws water from the extravascular space.