Biomedical subjects

R Busto

Publications and source records attributed to R Busto.

At least 163 records · Page 9Linked to original sources

PubMed1987

Histopathological and hemodynamic consequences of complete versus incomplete ischemia in the rat.

The primary objective of this study was to compare the histopathological consequences of complete versus incomplete ischemia under experimental conditions that limit lactate accumulation. Fasted rats underwent 1 h of either complete or incomplete ischemia by a procedure combining bilateral common carotid artery occlusion, halothane-induced systemic hypotension, and CSF pressure elevation. Histopathological outcome was evaluated 4 h later and was graded on a 4-point scale. Incomplete ischemia resulted in ischemic neuronal damage within selectively vulnerable brain regions. In contrast, complete ischemia, in addition to diffuse neuronal damage, resulted in focal sites of parenchymal necrosis with vascular stasis. Perfusion defects were detected by carbon black infusion within cortical and subcortical regions following only 25 min of complete, but not incomplete, ischemia. Ultrastructural abnormalities at the same duration of complete ischemia included a high frequency of endothelial microvilli and compressed lumina with severe perivascular astrocytic swelling. When recirculation was instituted for 1 h following 1 h of complete ischemia, regions of nonperfusion were detected autoradiographically. Thus, when the degree of lactic acidosis is controlled, prolonged periods of complete ischemia result in a more severe pathological outcome compared to incomplete ischemia. Focally impaired postischemic cerebral perfusion appears to be an important factor in infarct formation under the present experimental conditions.

Animals↗

PubMed1987

Cerebral phosphoinositide and energy metabolism during and after insulin-induced hypoglycemia.

During and after insulin-induced hypoglycemia, changes in levels of cerebral phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidic acid (PA), triacylglycerol (TAG), diacylglycerol (DAG), and free fatty acids (FFAs) as well as the cerebral energy state were studied in relation to the EEG. In hypoglycemic rats with an EEG pattern of quasiperiodic sharp or slow sharp waves, which preceded the development of an isoelectric EEG, PIP2 levels increased significantly, together with a slight decrease in PI content. Levels of the other lipids did not change during this period. The cerebral energy state was affected only slightly in spite of profound decreases in plasma and tissue glucose levels. With 30 min of an isoelectric EEG, levels of all phosphoinositides and PA decreased significantly; total FFA and DAG contents increased seven- and twofold, respectively; the TAG-palmitate level decreased, and that of TAG-arachidonate increased. Plasma and tissue glucose were nearly depleted, and the cerebral energy state deteriorated severely. The increment in fatty acids in the DAG and FFA pools was less than their loss from phosphoinositides and PA, an observation suggesting vascular washout or oxidation of a portion of the FFAs produced. Following 90 min of glucose infusion, PIP and PA levels recovered to control values; however, the PIP2 content exceeded control levels, and that of PI remained below control levels. DAG and FFA contents returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Seizure-associated pulmonary edema and cerebral oxygenation in the rat.

Cerebral partial pressure of O2 (PO2), relative changes in the ratio of reduced/oxidized cytochrome aa3, blood flow, and the arteriovenous difference in O2 content were measured during seizures with and without pulmonary edema. Seizures were induced with bicuculline (0.2-1.2 mg/kg iv) in rats anesthetized with 70% N2O and paralyzed with curare. Briefer seizures were accompanied by increased cerebral PO2 and increased oxidation of cytochrome aa3. Lung water content and arterial O2 partial pressure (PaO2) remained normal. Longer duration seizures were also accompanied initially by increases in cerebral oxygenation. Within minutes, however, PaO2 fell from a mean of 118 to 51 mmHg, and lung water content increased from 76.2 to 83.6%. Cerebral PO2 fell but most often rose back to or above control levels, while cytochrome aa3 became markedly reduced. Simultaneously, cerebral blood flow increased more than 300% above preseizure values and O2 delivery increased more than O2 consumption. The reductive shift of cytochrome aa3 was greater than that produced by lowering PaO2 to equivalent values in seizure-free rats. The reductive shift of cytochrome aa3, despite increased O2 delivery, may be indicative of derangements in cerebral O2 diffusion or energy metabolism.

Animals↗

PubMed1987

Coupled forebrain increases of local cerebral glucose utilization and blood flow during physiologic stimulation of a somatosensory pathway in the rat: demonstration by double-label autoradiography.

To investigate the relationships of local cerebral glucose utilization (lCMRgl) and blood flow (lCBF) during physiologic activation, awake Wistar rats received unilateral stimulation of the large facial whiskers (vibrissae) and were studied by carbon-14 double-label autoradiography. Activation was followed by increased lCMRgl and lCBF in appropriate forebrain structures. There was an overall preservation of metabolism/blood flow coupling during periods of somatosensory activation despite small but significant increases (14 to 22%) in the coupling ratio of the barrel field. Prolonged activation may give rise to an intracortical redistribution of lCBF within the barrel field.

Animals↗

PubMed1987

Role of dopamine in ischemic striatal injury: metabolic evidence.

We studied the effect of a prior unilateral substantia nigra lesion on the recovery of local cerebral glucose utilization (lCMRgl) and blood flow (lCBF), measured autoradiographically, following 30 minutes of forebrain ischemia in rats. On the lesioned side, striatal dopamine (DA) and its metabolites were depleted by more than 95% and did not change after ischemia. In contrast, significant increases in striatal DA metabolites occurred on the nonlesioned side following ischemia. Despite unilateral DA depletion, no side-to-side lCBF differences were observed. However, the normally occurring postischemic restoration of lCMRgl in the dorsolateral striatum at 2 and 4 hours of recirculation was suppressed on the DA-depleted side, and the degree of lCMRgl/lCBF uncoupling diminished. These results suggest that integrity of the DA system accentuates postischemic metabolism/flow uncoupling in the striatum and may therefore contribute to selective ischemic injury of this structure.

Animals↗

PubMed1986

Photochemically induced cortical infarction in the rat. 1. Time course of hemodynamic consequences.

Alterations in local CBF (LCBF) were assessed autoradiographically in the rat at several time points following photochemically induced cortical infarction. Cortical infarction of consistent size and location was produced by irradiating the brain with green light through the intact skull for 20 min following the systemic injection of rose bengal. A consistent pattern of altered LCBF was recorded in both ipsilateral and contralateral brain regions over the course of the study. At 30 min, a severely ischemic zone surrounded by regions of cortical hyperemia was apparent. LCBF was also depressed relative to control values in ipsilateral cortical regions remote from the irradiated area, while contralateral cortical structures were mildly hyperemic. By 4 h, the zone of severe ischemia had enlarged and its margins were no longer hyperemic. Ipsilateral cortical and some subcortical structures demonstrated significantly depressed levels of LCBF. At 5 days, LCBF throughout both ipsilateral and contralateral cortices was depressed compared with control values. By 15 days, LCBF had returned to control levels in most brain structures shown histopathologically not to be irreversibly damaged. The temporal sequence and magnitude of these hemodynamic alterations are consistent with findings in clinical studies in which repeated measurements of CBF have been carried out in patients with acute stroke. The ability to produce a cortical infarct that results in a consistent pattern of altered CBF should facilitate the investigation of stroke mechanisms responsible for these hemodynamic abnormalities.

Animals↗

PubMed1986

Photochemically induced cortical infarction in the rat. 2. Acute and subacute alterations in local glucose utilization.

Local CMRglu (LCMRglu) values were measured by [14C]2-deoxyglucose autoradiography in the rat at 4 h and 5 days following photochemically induced cortical infarction, and these data were compared with neuropathological findings in adjacent serial sections. At both time periods, LCMRglu was markedly reduced within the lesion center, and irregular regions of moderate-to-marked glucose hypermetabolism were noted within the marginal zone of the developing infarct. At 4 h, the hypermetabolic zones were shown by pathological examination to be characterized by normal-sized, moderately hyperchromatic neurons scattered among occasional dark, shrunken neurons within preserved neuropil. In contrast, the hypermetabolic zones at 5 days coincided with foci of intense macrophage infiltration, with dissolution of the neuropil. Significant decreases in glucose utilization were also demonstrated at 4 h within brain structures remote from the site of focal injury. These structures included the lateral and auditory cortices ipsilaterally, the striatum and thalamus ipsilaterally, and the hippocampus bilaterally. In addition to these remote metabolic effects, depressed metabolism occurred within the homologous cortical region contralateral to the site of infarction. By 5 days, glucose utilization was severely depressed in all ipsilateral cortical regions but not within any contralateral cortical region. Analysis of these data suggests that more than one mechanism is responsible for the metabolic alterations occurring within brain regions remote from the site of irreversible damage. Results are discussed in light of the hemodynamic alterations occurring in this stroke model, which are presented in the accompanying report.

Animals↗

PubMed1986

Simultaneous determination of local cerebral glucose utilization and blood flow by carbon-14 double-label autoradiography: method of procedure and validation studies in the rat.

Validation studies were undertaken to establish a computer-assisted double-label autoradiographic strategy employing [14C]2-deoxyglucose ([14C]2DG) and [14C]iodoantipyrine ([14C]IAP) to measure local CMRglu (LCMRglu) and CBF (LCBF). An organic solvent was used to extract the majority of IAP between first and second film exposures. In contrast to previously published data, all solvents tested produced partial losses of 2DG from tissue, and all allowed 2-6% of IAP to persist even after 5-day washes. Technical-grade chloroform permitted equal retention of unmetabolized and metabolized 2DG. A linear model was established, which was insensitive to the changes in tissue self-absorption that were shown to occur with chloroform extraction. Propagated error in computing tissue [14C]2DG and [14C]IAP was reduced by maximizing IAP extraction (by longer solvent wash times) and by administering 2.5 times as much IAP as 2DG. Fractional 2DG retention was measured in single-label 2DG sections placed on the films, and fractional IAP retention was evaluated by an optimization procedure. With this strategy, double-label values for LCMRglu and LCBF in anesthetized rats agreed with values obtained in matched single-label series to within 5%. The coefficients of variation for the double- and single-label LCMRglu data were virtually identical, whereas the coefficient of variation for double-label LCBF was 1.8 times that of single-label LCBF. The double-label strategy permitted pixel-by-pixel measurement and video display of the LCMRglu/LCBF ratio; the mean value among structures was 0.472 mumol/ml. With proper attention to methodological detail, this double-label strategy shows great promise for routine laboratory application.

Animals↗

PubMed1986

Effect of transient cerebral ischemia on metabolic activation of a somatosensory circuit.

The effects of transient ischemia on the metabolic responsiveness of a well-defined brain circuit were investigated with [14C]2-deoxyglucose autoradiography. Rats underwent 30 min of severe forebrain ischemia followed by postischemic recirculation periods of 1, 2, 3, 5, and 10 days. At these times, unilateral whisker stimulation was carried out, resulting in the metabolic activation of the whisker barrel circuit. An altered pattern of glucose utilization within both stimulated and nonstimulated circuit relay stations was observed at 1, 2, and 3 days following ischemia. At 1 day, stimulus-evoked increases in metabolic activity were severely depressed within both the ventrobasal thalamus and layer IV of the cortical barrel field region. Baseline metabolic rate within nonstimulated relay areas was also severely depressed at this time. At postischemic days 2 and 3, moderate levels of increased glucose utilization were apparent overlying cortical layer IV and the superficial half of layer VI, while layers I, II, III, and V appeared less responsive to metabolic activation. By day 5, whisker stimulation resulted in normal levels of increased glucose utilization within the activated ventrobasal thalamus and layer IV of the cortical barrel field region. Glucose utilization within nonactivated relay stations, depressed at earlier time periods, had also returned to control levels by day 5. At both 5 and 10 days, an altered laminar pattern of elevated glucose utilization was apparent within the activated barrel field region, with local CMRglu being depressed in layer V compared with control values. These results demonstrate that periods of transient ischemia produce both reversible and longer-lasting effects on the ability of the CNS to respond to peripheral activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Vascular aspects and hemodynamic consequences of central nervous system injury.

We document here microvascular alterations occurring in models of mild, moderate, and severe cerebral ischemic injury. The relationship of the vascular abnormalities to the generation of hemodynamic alterations was also evaluated. Following periods of severe incomplete ischemia, scanning electron microscopic analysis of cerebral microvessels revealed the widespread production of cerebral endothelial microvilli. These microvilli increased in frequency as the ischemic insult was prolonged and remained prominent during periods of recirculation. Although these luminal projections would not be expected to inhibit reperfusion completely, they might increase microvascular resistance, leading to moderate hemodynamic impediments extending into the post-ischemic period. Similar periods of complete ischemia resulted in more severe microvascular alterations. Light and electron microscopic studies revealed a high frequency of compressed capillary lumina with vascular stasis. These compressed vessels were consistently surrounded by swollen astrocytic foot processes. When recirculation was instituted for 1 hr following 1 hr of complete ischemia, regions of non-perfusion were detected autoradiographically within brain regions destined to undergo ischemic infarction. Finally, in an attempt to determine the consequences of a primary microvascular insult on brain structure and function, the endothelial layer of microvessels in the cerebral cortex was injured using a noninvasive photochemical method. Endothelial damage led to platelet aggregation in both pial and intraparenchymal vessels. Occlusive thrombi were frequently detected with perivascular edema associated with vascular compression and severe focal ischemia. Ultrastructural blood-brain barrier studies using the horseradish peroxidase tracer demonstrated that protein leakage at the site of primary vascular injury resulted in tracer material in brain regions remote from the pathological lesion. The widespread leakage of protein tracer was associated with decreased blood flow in remote brain regions at several postirradiation periods. These data emphasize the importance of injury-induced microvascular dysfunction in the generation of brain lesions and hemodynamic abnormalities.

Animals↗

PubMed1986

Cerebral phosphoinositide, triacylglycerol, and energy metabolism in reversible ischemia: origin and fate of free fatty acids.

Levels of phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol (PI), phosphatidic acid, diacylglycerol (DAG), triacylglycerol (TAG), and free fatty acids (FFAs), as well as their fatty acid composition, were determined in rat forebrain during ischemia and postischemic recirculation. Cerebral energy state and electroencephalograms (EEGs) were also studied. Fifteen minutes of ischemia resulted in a decrease in PIP2 and PIP contents but not in PI content, concurrent with an enlargement of the FFA and DAG pools. The latter were enriched in stearate and arachidonate. Prolongation of ischemia did not produce further changes in content of any of the inositol phospholipids, but the increase in levels of FFAs and DAG continued. At the end of 45 min of ischemia, levels of both PIP2 and PIP decreased by 45-50%, and the total phosphoinositide content (PIP2 + PIP + PI) decreased by 21%, whereas levels of FFAs and DAG increased to 14- and 3.6-fold of control levels, respectively. During ischemia, the TAG-palmitate level decreased, but the TAG-arachidonate level increased; the tissue energy state deteriorated severely; and the EEG was suppressed. A 30-min recirculation period after 15 or 45 min of ischemia led to increases in PIP2, PIP, and total phosphoinositide contents, whereas levels of FFAs and DAG promptly decreased toward control values. The TAG-arachidonate level peaked and the TAG-palmitate level returned to a low control value during early recirculation. The ischemic changes in tissue lipids were completely reversed within 3 h of recirculation after both periods of ischemia. Adenylates were fully phosphorylated with as little as 30 min of reflow. The EEG activity partially recovered during reflow after 15 min of ischemia, whereas it remained depressed after prolonged ischemia. Thus, phosphodiesteric cleavage of PIP2 and PIP followed by deacylation of DAG is likely to contribute to the production of FFAs in early ischemia. Deacylation of undetermined lipids plays a role for the increment in levels of FFAs in the later period of ischemia. The rapid postischemic increase in levels of PIP2 and PIP indicates active synthesis not only from existing PI, but probably also by means of accumulated FFAs and DAG. These results indicate that the impaired resynthesis of inositol phospholipids cannot be a cause of the poor EEG activity after prolonged ischemia. Degradation and resynthesis of polyphosphoinositides and formation of TAG-arachidonate may be important for modulation of free arachidonic acid levels in the brain during temporary ischemia.

Animals↗

PubMed1986

Polyphosphoinositides as a probable source of brain free fatty acids accumulated at the onset of ischemia.

The quantitative relationship between phosphoinositides and free fatty acids (FFAs) in brain ischemia was studied by measuring contents of individual fatty acids in phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol (PI), phosphatidic acid (PA), diacylglycerol (DAG), and the FFA pool. Various periods of complete ischemia (1, 3, 10, and 30 min) were produced by decapitation. Ischemia of 1-3 min caused rapid decreases in PIP2 and PIP content together with preferential production of stearic and arachidonic acids in the DAG and FFA pools. The decrement in levels of these fatty acid residues in polyphosphoinositides was sufficient to account for their increment in levels in the enlarged DAG and FFA pools. After 10 min of ischemia, levels of PIP2, PIP, and DAG approached plateau values, but levels of all FFAs continued to increase. The increases in content of DAG and FFAs at later ischemic periods could not be accounted for by the decreases in content of PIP2 and PIP, PI and PA levels showed only transient and subtle changes. These results indicate that, at the onset of ischemia, phosphodiesteric cleavage of PIP2 and PIP and subsequent deacylation by lipases are primarily responsible for the preferential increase in levels of free stearic and arachidonic acids and that, later, hydrolysis of other phospholipids plays a major role in the continuous accumulation of FFAs.

Animals↗

PubMed1986

Monoamine neurotransmitters in diffuse reversible forebrain ischemia and early recirculation: increased dopaminergic activity.

Regional levels of brain monoamines and their metabolites were examined in a rat model of reversible and diffuse forebrain ischemia with and without reperfusion. During ischemia, blood flow decreased by 87 to 95%, but recovered to control values during recirculation. Norepinephrine and serotonin decreased in the cerebral cortex and hippocampus during ischemia and diminished further during recirculation. On the other hand, dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, which were not much affected by ischemia, increased markedly in the cerebral cortex and striatum during recirculation, with a decrease in the ratio of dopamine to its metabolites. These results suggest central dopaminergic hyperactivity during recirculation, which may be related to the selective vulnerability of the striatum in similar models of reversible forebrain ischemia.

Animals↗

PubMed1985

Regional blood-brain barrier permeability to water and cerebral blood flow during status epilepticus: insensitivity to norepinephrine depletion.

To test whether status epilepticus alters regional blood-brain barrier (BBB) permeability to water when systemic hypertension is avoided, and whether central noradrenergic innervation contributes to the regulation of BBB in this setting, Wistar rats with unilateral 6-hydroxydopamine lesion of the nucleus locus coeruleus (LC) were subjected to 8 min of bicuculline-induced status epilepticus while ventilated with 100% oxygen; arterial normotension was preserved by withdrawal of arterial blood as required. Regional cerebral blood flow and permeability-times-surface-area product (PS) for water were measured by a double-label modification of the Kety integral strategy, with [14C]butanol and [3H]water, respectively. In normocapnic control rats, regional cerebral blood flow (rCBF) was 1.92 +/- 0.57 ml/g/min and water extraction fraction was 0.81 +/- 0.08 (S.D.). Values in control rats breathing 100% oxygen were similar. During status epilepticus, rCBF increased two- to three-fold; water extraction fraction declined, but there were no significant side-to-side differences for either rCBF or regional PS product for water in LC-lesioned animals despite an 81% reduction of cortical norepinephrine content on the lesioned side. The PS product for water increased by 42% during status epilepticus, but the flow vs PS-product relationship did not depart from that predicted on the basis of data in control rats. Thus, when systemic hypertension is prevented, brief status epilepticus does not induce abnormal BBB permeability to water, and unilateral LC lesion fails to influence either rCBF or the cerebrovascular PS product for water.

Animals↗

PubMed1985

Induction of reproducible brain infarction by photochemically initiated thrombosis.

We have used a photochemical reaction in vivo to induce reproducible thrombosis leading to cerebral infarction in rats. After the intravenous injection of rose bengal, a potent photosensitizing dye, an ischemic lesion was formed by irradiating the left parietal convexity of the exposed skull for 20 minutes with green light (560 nm) from a filtered xenon arc lamp. Animals were allowed to survive from 30 minutes to 15 days after irradiation. Early microscopic alterations within the irradiated zone included the formation of thrombotic plugs and adjacent red blood cell stasis within pial and parenchymal vessels. Scanning electron microscopy revealed frequent platelet aggregates adhering to the vascular endothelium, often resulting in vascular occlusion. Carbon-black brain perfusion demonstrated that occlusion of vascular channels progressed after irradiation and was complete within 4 hours. Histopathological examination at 1, 5, and 15 days revealed that the associated infarct evolved reproducibly through several characteristic stages, including a phase of massive macrophage infiltration. Although cerebral infarction in this model is initiated by thrombosis of small blood vessels, the fact that the main pathological features of stroke are consistently reproduced should permit its use in assessing treatment regimens. Further, the capability of producing infarction in preselected cortical regions may facilitate the study of behavioral, functional, and structural consequences of acute and chronic stroke.

Animals↗

PubMed1985

Cerebral norepinephrine depletion enhances recovery after brain ischemia.

Monoamine neurotransmitters, especially norepinephrine (NE), may have an important role in the pathophysiological aspects of postischemic cerebral dysfunction. In previous studies of post-decapitation-induced ischemia, we found that NE depletion caused a delay in glycogen breakdown but did not influence any of the other known biochemical abnormalities that accompany brain ischemia. In this study, we have turned to a model of transient incomplete and diffuse forebrain ischemia in the rat to examine the effects of cerebral NE depletion on the recovery after brain ischemia of levels of high-energy phosphate compounds, products of intermediary oxidative metabolism, and free fatty acids. We found that a unilateral lesion of the locus ceruleus and the resultant depletion of NE in the ipsilateral cerebral cortex had no effect on sham-operated controls nor on rats subjected to ischemia alone. However, in rats subjected to ischemia followed by 15 minutes of recirculation, the NE-depleted cerebral cortex had significantly higher phosphocreatine and adenosine triphosphate levels and energy charge, and lower adenosine monophosphate and docosahexaenoic acid concentrations. With longer periods of recirculation, these side-to-side differences were not apparent. These results suggest that activity of the central NE systems during transient brain ischemia has deleterious effects on the biochemical recovery of the cerebral cortex from severe ischemic insults.

Adenosine Monophosphate↗

PubMed1985

Regional glucose utilization and blood flow following graded forebrain ischemia in the rat: correlation with neuropathology.

Regional patterns of cerebral glucose utilization (rCMRglc) and blood flow (rCBF) were examined in the early recovery period following transient forebrain ischemia in order to correlate early postischemic physiological events with regionally selective patterns of ischemic neuropathology. Wistar rats were subjected to 30 or 60 minutes of graded forebrain ischemia by a method combining unilateral occlusion of the common carotid artery with moderate elevation of intracranial pressure and mild hypotension; this procedure results in a high-grade ischemic deficit affecting chiefly the lateral neocortex, striatum, and hippocampus ipsilateral to the carotid occlusion. Simultaneous measurements of rCMRglc and rCBF made in regional tissue samples after 2 and 4 hours of postischemic recirculation using a double-tracer radioisotopic strategy revealed a disproportionately high level of glucose metabolism relative to blood flow in the early postischemic striatum, owing to the resumption of nearly normal rCMRglc in the face of depressed flow. In contrast, the neocortex, which had been equally ischemic, showed parallel depressions of both metabolism and blood flow during early recovery. Light microscopy at 4 and 8 hours after recovery revealed the striatum to be the predominant locus of ischemic neuronal alterations, whereas neocortical lesions were much less prominent in extent and severity at this time. The resumption of normal levels of metabolism in the setting of a disproportionate depression of rCBF in the early postischemic period may accentuate the process of neuronal injury initiated by ischemia and may contribute to the genesis of neuronal necrosis in "selectively vulnerable" areas of the forebrain.

Animals↗

PubMed1985

Regional brain energy metabolism after complete versus incomplete ischemia in the rat in the absence of severe lactic acidosis.

Levels of energy metabolites were measured in forebrain regions in fasted rats subjected to 4-h recirculation after 1 h of either incomplete or complete ischemia. Both models of ischemia were produced by a procedure combining bilateral common carotid artery occlusion, systemic hypotension, and CSF pressure elevation; the degree of intracranial hypertension was varied to produce incomplete and complete ischemia. Levels of brain lactate at the end of ischemia ranged from 16 to 19 mmol/kg in incomplete ischemia and from 11 to 13 mmol/kg in complete ischemia. Energy metabolism recovered evenly in the neocortical and subcortical regions with recirculation after incomplete ischemia. The metabolic recovery in the cerebral cortex after complete ischemia was similar to that observed after incomplete ischemia; however, recovery in the subcortical regions after complete ischemia was less extensive, NADH fluorescence remained high, and there was a fall in total creatine. Intracellular pH in the dorsal thalamus was more alkalotic after complete than incomplete ischemia. Thus, in the absence of profound tissue lactic acidosis, residual CBF during prolonged ischemia helps postischemic restitution of brain energy metabolism in subcortical regions. The pattern of poor recovery in these regions after complete ischemia suggests inadequate reperfusion. The decreased total creatine and the severe tissue alkalosis may be biochemical markers of advanced tissue injury during reflow.

Acidosis↗