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J H Garcia

Publications and source records attributed to J H Garcia.

At least 19 recordsLinked to original sources
PubMed2001

Analysis of temporal and spatial dichotomous PM air samples in the El Paso-Cd. Juarez air quality basin.

This paper presents and discusses the results obtained from the gravimetric and chemical analyses of the 24-hr average dichotomous samples collected from five sites in the El Paso-Cd. Juarez air quality basin between August 1999 and March 2000. Gravimetric analysis was performed to determine the temporal and spatial variations of PM2.5 (particulate matter less than 2.5 microm in diameter) and PM25-10 (particulate matter less than 10 pm but greater than 2.5 microm in diameter) mass concentrations. The results indicate that approximately 25% of the PM10 (i.e., PM25 + PM25-10) concentration is composed of PM2.5. Concurrent measurements of hourly PM concentrations and wind speed showed strong diurnal patterns of the regional PM pollution. Results of X-ray fluorescence (XRF) elemental analyses were compared to similar but limited studies performed by the Texas Natural Resource Conservation Commission (TNRCC) in 1990 and 1997. Major elements from geologic sources-Al, Si, Ca, Na, K, Fe, and Ti-accounted for 35% of the total mass concentrations in the PM2.5-10 fraction, indicating that geologic sources in the area are the dominant PM sources. Levels of toxic trace elements, mainly considered as products of anthropogenic activities, have decreased significantly from those observed in 1990 and 1997.

Air Pollutants↗
PubMed2001

Regional variations in the apparent diffusion coefficient and the intracellular distribution of water in rat brain during acute focal ischemia.

BACKGROUND AND PURPOSE: The apparent diffusion coefficient of water (ADC) rapidly drops in ischemic tissue after cerebral artery occlusion. This acute drop is thought to be caused by the loss of extracellular fluid and the gain of intracellular fluid. To test the latter possibility, changes in ADC and the size of several cellular compartments were assessed in 3 regions of rat brain at the end of 90 minutes of focal cerebral ischemia. METHODS: One middle cerebral artery was permanently occluded in 8 Sprague-Dawley rats; sham occlusions were performed in 2 other rats. ADC maps were generated 90 minutes later, and the brains were immediately perfusion fixed. Three regions of interest (ROIs) were defined on the basis of ADC range. Various neuronal, astrocytic, and capillary compartments in each ROI were quantified with light and electron microscopy. RESULTS: At the end of 90 minutes of ischemia, mean ADC was normal in the cortex of sham-operated rats and the contralateral cortex of ischemic rats (ROI-a), 25% lower in the ipsilateral frontoparietal cortex (ROI-b), and 45% lower in the ischemic lateral caudoputamen (ROI-c). At this time, the frequency of swollen astrocytic cell bodies and volume of swollen dendrites and astrocytic processes in neuropil were ROI-a<ROI-b<ROI-c. In ROI-b and ROI-c, 40% and 60% of the neurons, respectively, were shrunken; the shrunken neurons were approximately 25% smaller in ROI-c than in ROI-b. In these areas, many capillary endothelial cells, pericytes, and perivascular foot processes were swollen. CONCLUSIONS: The initial lowering of ADC during focal ischemia probably is the result of not only the acute loss of extracellular fluid and concomitant swelling of various cellular compartments but also concurrent neuronal shrinkage.

Acute Disease↗
PubMed1999

Reversal of acute apparent diffusion coefficient abnormalities and delayed neuronal death following transient focal cerebral ischemia in rats.

Twenty-two rats were subjected to 8, 15, 30, or 60 minutes of temporary middle cerebral artery occlusion (n = 5 per group) or sham occlusion (n = 2) in the magnetic resonance imaging unit. Diffusion-, perfusion-, and T2-weighted imaging were acquired before and during occlusion, and after reperfusion. A coregistration method was used to correlate the acute changes of the average apparent diffusion coefficient (ADCav) with the histology after 72 hours at the same topographic sites. The initially reduced ADCav values recovered completely in both the lateral caudoputamen and upper frontoparietal cortex in the 8-, 15-, and 30-minute groups, partially in the cortex, and not at all in the caudoputamen in the 60-minute group. The histology showed that the caudoputamen was either normal or had mild neuronal injury in the 8-minute group and invariably had some degree of neuronal death in the 15-, 30-, and 60-minute groups, whereas the cortex was either normal or had varying degrees of neuronal injury in all groups. No histological abnormalities were seen in the sham-operated rats. Our data suggest that acute ADCav reversal does not always predict tissue recovery from ischemic injury and that temporary focal ischemia for even 8-minute duration can cause delayed neuronal death that is more severe in the caudoputamen where the initial ADCav decline was greater than in the cortex.

Animals↗
PubMed1999

Hemorrhagic transformation in focal cerebral ischemia: influence of time to artery reopening and tissue plasminogen activator.

We used an adaptation of a well-established rat model of middle cerebral artery occlusion (MCAO) that is both minimally invasive and reproducible to determine the effects of time to reperfusion and administration of tissue plasminogen activator (t-PA) on the development of hemorrhagic transformation (HT) in a rat model of acute stroke. Animals were randomized to receive either t-PA 10 mg/kg (29 rats) or an equal volume of saline (29 rats) over 20 minutes, beginning 5 minutes before reperfusion. Time to artery reopening varied between 1 and 24 hours after MCAO in both groups. At 18-24 hours after ischemia, the animals were sacrificed and their brains were preserved for analysis of HT. Logistic regression was used to determine the influence of time on HT risk and calculate the time at which 50% of animals developed HT (HT50%). At 24 hours, HT was present in 17 of 29 animals in each group and was significantly influenced by the time of artery reopening: 3 (15%) of 20 animals reperfused less than 3 hours after onset of ischemia and 32 (84%) of 38 reperfused 3 or more hours after the onset of ischemia (p<0.001). There was no difference in HT50% between groups. Time to artery reopening is an important determinant of HT risk in this model of cerebral ischemia. This model may have utility in developing strategies to reduce HT formation after thrombolytic therapy in patients with acute stroke.

Animals↗
PubMed1997

Cognitive impairment and cellular/vascular changes in the cerebral white matter.

A possible relation between cerebral white-matter injury and dementia was intuitively attributed by Alzheimer to changes affecting the small penetrating vessels that supply the cerebral white matter. Several observations support the view that white-matter changes detectable by neuroimaging may contribute to cognitive deficits in the elderly. But many questions concerning this matter remain partially answered. In this communication we review: (1) Selected anatomic features of the blood vessels supplying the white matter; (2) possible pathogenetic mechanisms responsible for the white-matter changes; (3) observations on humans and animals suggesting a causal relationship between ischemia/hypoxemia and white-matter injury; (4) epidemiologic studies linking white-matter abnormalities with cognitive disorders. We conclude that abnormalities in the small vessels caused by aging and arterial hypertension, or other processes (cerebral amyloid angiopathy, CADASIL) together with systemic circulatory disturbances, such as abrupt variations in blood pressure values or cardiac diseases, may be the substrate of selective white-matter injury. The damage is structurally characterized by incomplete infarction or selective cellular injury.

Alzheimer Disease↗
PubMed1997

Incomplete infarct and delayed neuronal death after transient middle cerebral artery occlusion in rats.

BACKGROUND AND PURPOSE: The clinical syndrome of transient ischemic attacks is accompanied in a significant percentage of patients by brain lesions or neuroimaging abnormalities whose structural counterparts have not been defined. The objective of this study was to analyze, in an experimental model of short-term (< 25 minutes) focal ischemia and long-term (< or = 28 days) reperfusion, the extent and nature of the structural abnormalities affecting neurons and glia located within the territory of the transiently occluded artery. METHODS: Adult Wistar rats (n = 121) had the origin of one middle cerebral artery (MCA) occluded with a nylon monofilament for periods of 10 to 25 minutes. Experiments of transient MCA occlusion were terminated at variable periods ranging from 1 day to 4 weeks. Control experiments consisted of (1) MCA occlusion without reperfusion (n = 7) lasting 7 to 14 days and (2) sham operations (n = 2) followed by 1- to 4-day survival. After in situ fixation, brain specimens were serially sectioned and subjected to detailed morphometric evaluations utilizing light and electron microscopes. The statistical method used to evaluate the results was based on ANOVA followed by Bonferroni's corrected t test and Student's t test comparisons. RESULTS: Brain lesions were not detectable in the sham-operated controls. All brains with permanent MCA occlusion (7 to 14 days) had large infarctions with abundant macrophage infiltration and early cavitation. Forty-five (37%) of the experiments involving transient MCA occlusion had no detectable brain lesions after 4 weeks. Selective neuronal necrosis was found in 76 of 121 rats (63%) with transient MCA occlusion. Neuronal necrosis always involved the striatum, and in 29% of the brains with ischemic injury, necrosis also included a short segment of the cortex. In the striatum, the length of the arterial occlusion was the main determinant of the number of necrotic neurons (20 minutes [22.6 +/- 19] is worse than 10 minutes [4.9 +/- 7]) (P < .0001). In the cortex, the length of reperfusion determined the number of necrotic neurons appearing in layer 3. Experiments with reperfusion of 4 to 7 days' duration yielded more necrotic neurons per microscopic field (2.02 +/- 3) than those lasting fewer days (0.04 +/- 0.1) (P < .05). The histological features of these lesions underwent continuous change until the end of the fourth week, at which time necrotic neurons were still visible both in the striatum and in the cortex. CONCLUSIONS: Arterial occlusions of short duration (< 25 minutes) produced, in 76 of 121 experiments (63%), brain lesions characterized by selective neuronal necrosis and various glial responses (or incomplete infarction). This lesion is entirely different from the pannecrosis/cavitation typical of an infarction that appears 3 to 4 days after a prolonged arterial occlusion. Delayed neuronal necrosis, secondary to a transient arterial occlusion or increasing numbers of necrotic neurons in experiments with variable periods of reperfusion, was a response observed only at a predictable segment of the frontoparietal cortex.

Animals↗
PubMed1997

Pathogenesis of leukoaraiosis: a review.

BACKGROUND: Changes in the cerebral hemispheric white matter, detectable with increasing frequency by modern neuroimaging methods, are associated with aging and conceivably may contribute to the development of specific cognitive deficits. The pathogenesis of these cerebral white matter abnormalities (sometimes described as leukoaraiosis) is unknown. This review evaluates the available evidence in support of the hypothesis that the etiology of leukoaraiosis is related to a specific type of cerebral ischemia and highlights mechanisms by which ischemic injury to the brain may induce selected structural alterations limited to the cerebral white matter. SUMMARY OF REVIEW: The review is based on the critical analysis of over 100 publications (most appearing in the last decade) dealing with the anatomy and physiology of the arterial circulation to the cerebral white matter and with the pathogenesis of leukoaraiosis. CONCLUSIONS: A significant number of clues support the hypothesis that some types of leukoaraiosis may be the result of ischemic injury to the brain. Structural changes affecting the small intraparenchymal cerebral arteries and arterioles that are associated with aging and with stroke risk factors, altered cerebral blood flow autoregulation, and the conditions created by the unique arterial blood supply of the hemispheric white matter each seem to contribute to the development of leukoaraiosis. To the best of our ability to interpret current information, the type of ischemic injury that is most likely responsible for these white matter changes involves transient repeated events characterized by moderate drops in regional cerebral blood flow that induce an incomplete form of infarction. This hypothesis could be tested in appropriate experimental models.

Brain Diseases↗
PubMed1997

DNA scission after focal brain ischemia. Temporal differences in two species.

BACKGROUND AND PURPOSE: Species- and model-dependent differences in cell response to focal brain ischemia may underlie differences in adhesion receptor expression. The aim of this study was to quantitatively evaluate the spatial and temporal distribution of dUTP incorporation into damaged DNA, as an indicator of ischemic injury, in the corpus striatum. METHODS: Cerebral ischemia was produced in 16 nonhuman primates and 19 rats by occluding the middle cerebral artery (MCA:O) with reperfusion for various periods. In situ dUTP was incorporated into cells with DNA damage by terminal deoxynucleotidyl transferase (TdT), DNA polymerase I, or the Klenow fragment of DNA polymerase. Dual immunolabeling experiments with immunoprobes against neuronal, vascular, or glial marker proteins were performed. RESULTS: Significant topographical differences in dUTP between the two species were seen. In both models the TdT and polymerase I regions changed characteristically during focal ischemia. The number and density of dUTP-labeled cells increased with time from MCA:O and were dramatically different between the species (2P < .001). By 2 hours of ischemia, the density of dUTP label was 48.8 +/- 10.3 cells/mm2 in the primate and 2.4 +/- 0.8 cells/mm2 in the rat (2P < .05), but these values became nearly identical by 24 hours of reperfusion. In the primate, 80.0 +/- 6.6% of labeled cells displayed microtubule-associated protein-2 antigen (at 2-hour MCA:O), while 1.8 +/- 0.5% were associated with microvessels at 24 hours of reperfusion. CONCLUSIONS: In situ detection of DNA damage, accomplished by three methods, reveals distinct temporal, topographical, and density differences in ischemic injury to cells in the primate and the rat corpus striatum as a result of MCA:O.

Animals↗
PubMed1996

Vascular pathology in three cases of progressive cognitive deterioration.

The clinical condition known as vascular dementia remains poorly defined. Few studies have attempted a correlative link between the clinical syndrome and the structural abnormalities of the brain. Classically the clinical progression of the vascular dementing process is thought to be a multi-step process punctated by repeated episodes of ischemia, that are clinically expressed as strokes. In most instances it has been assumed that the substrate of vascular dementias consists of atherothrombotic infarcts. The objective of this report is to illustrate 3 cases of progressive (rather than stepwise) cognitive deterioration without clinical evidence of stroke, evolving over a period of several years, in which there were prominent vascular lesions. A complete autopsy and detailed neuropathologic examination demonstrated cerebral vascular lesions involving small arterial vessels (< 200 microns in diameter). The lesions consisted of moderate-to-severe arteriolosclerosis in two cases, and mild-to-moderate arteriolosclerosis in a case of Alzheimer's disease with severe cerebral amyloid angiopathy. Parenchymal lesions consisted of small cortical and subcortical infarcts, most of them smaller than 0.1 cm in average diameter, and subcortical leukoencephalopathy severe in two cases and mild-to-moderate in the third case. Severe atherosclerosis not accompanied by large infarcts was also present in one case. Arterial changes affecting small, distal branches causing sometimes small parenchymal lesions in association with diffuse cerebral white matter disease, appear to be the anatomical substrate that accompanies progressive cognitive impairment in some patients who are frequently diagnosed with Alzheimer's disease because in their clinical records there is neither history of strokes nor stepwise progression of symptoms.

Aged↗
PubMed1996

Ischemic stroke and incomplete infarction.

BACKGROUND: The concept of selective vulnerability or selective loss o f individual neurons, with survival of glial and vascular elements as one of the consequences of a systemic ischemic-hypoxic insult (eg, transient cardiac arrest or severe hypotension), has been recognized for decades. In contrast, selective neuronal death as one of the lesions that may develop in the brain after occluding an intracranial artery is an idea not readily acknowledged in the current medical literature dealing with human stroke. SUMMARY OF REVIEW: A review of pertinent publications reveals that selective neuronal injury after middle cerebral artery occlusion was observed in autopsy specimens over 40 years ago, although its pathogenesis remains unclear. Recent observations in both humans and animals suggest that selective neuronal necrosis (rather than infarct) is the consequence of either a short-term arterial occlusion or permanent occlusion accompanied by ischemia of moderate severity. During the acute and subacute states of an ischemic stroke, the loss of a limited number of neurons (ie, incomplete infarction) does not result in structural changes discernible by either CT or conventional MRI. However, the loss of a selected number of neurons may be demonstrable in vivo by calculating the corresponding loss of benzodiazepine receptors. The use of specific radiotracers in combination with single-photon emission CT or positron emission tomography allows demonstration of a decrease in gamma-aminobutyric acid-ergic receptor sites at places where many neurons have been lethally injured. CONCLUSIONS: We aim to alert physicians to the potential development of incomplete brain infarctions in patients with intracranial arterial occlusions. Recognizing incomplete infarcts is particularly important in the context of stroke therapy with thrombolytic and neuroprotective agents. This brain lesion is likely to be the consequence of an arterial occlusion with a resultant ischemia of moderate severity (eg, regional blood flows in the range of 15 to 20 mL x 100 g-1 x min-1).

Animals↗
PubMed1996

Cerebral white matter is highly vulnerable to ischemia.

BACKGROUND AND PURPOSE: The effects of ischemia on the cerebral white matter structure seldom have been studied possibly because white matter is generally considered less vulnerable to ischemia than gray matter. The objective of this study was to evaluate the early (< or = 24 hours) structural effects of experimental focal ischemia on the cerebral white matter of the rat as a preliminary step to investigating human conditions of unknown pathogenesis that are characterized by selective damage to the white matter. METHODS: Twenty-eight rats, including four controls, had a middle cerebral artery occluded with an intravascular filament for periods ranging between 0.5 and 24 hours. Brain samples from the subcortical white matter were examined with light and electron microscopic methods, and the abnormalities were quantified with an image-analysis system. RESULTS: As early as 30 minutes after the arterial occlusion, there was conspicuous swelling of oligodendrocytes and astrocytes; after 3 hours, large numbers of oligodendrocytes were lethally injured. These changes preceded by several hours the appearance of necrotic neurons in the cortex and basal ganglia. Vacuolation and pallor of the white matter were very marked after 24 hours and reflected the segmental swelling of myelinated axons, the formation of spaces between myelin sheaths and axolemma and astrocyte swelling. CONCLUSIONS: These results suggest that the cerebral white matter is highly vulnerable to the effects of focal ischemia. Pathological changes in oligodendrocytes and myelinated axons appear early and seem to be concomitant with, but independent of neuronal perikaryal injury. Modifications of this experimental model of focal ischemia could provide the means to test the hypothesis that selected types of human leukoencephalopathies have an ischemic origin.

Animals↗
PubMed1996

Severe transient hypoglycemia causes reversible change in the apparent diffusion coefficient of water.

BACKGROUND AND PURPOSE: The aim of this study was to determine the effects of temporary severe hypoglycemia on the apparent diffusion coefficient (ADC) acquired by diffusion-weighted MRI of brain water with the use of serial multislice ADC mapping in rats. Severe hypoglycemia reduces the extracellular space volume, as does ischemia. Demonstrating a reduction of ADC with hypoglycemia should increase our understanding of the mechanisms underlying ADC changes in ischemia and other conditions. METHODS: Fasted rats were given regular insulin (15 IU/kg IP). Rats were subjected to 15 minutes (n = 5) and 50 minutes (n = 5) of temporary severe hypoglycemia, causing a transiently isoelectric electroencephalogram (EEG). ADC mapping was performed every 30 seconds beginning at the onset of isoelectricity for 8.5 minutes. ADC maps were also obtained later during the isoelectric EEG period and 10, 20, 30, and 40 minutes after glucose infusion. Control images were obtained from a separate group of animals suffering cardiac arrest (n = 5). RESULTS: Abnormal ADC values were not observed before the onset of cerebral isoelectricity, except for isolated areas in the cortex and periventricular regions. Cortical ADC values globally declined at the onset of EEG isoelectricity. The ADC decline spread to subcortical regions within a few minutes. During the isoelectric period, significant declines of ADC values (27% to 45%) occurred in the entire brain. Glucose infusion normalized most of the ADC changes, even after a 50-minute period of isoelectricity. CONCLUSIONS: ADC mapping during hypoglycemia clearly demonstrates changes likely related to energy depletion. Most of these ADC declines were reversible. Hypoglycemia is a condition known to be associated with shrinkage of the extracellular space. These observations support the hypothesis that ADC reductions observed in ischemia are also related to shifts of water from the extracellular to the intracellular compartment.

Animals↗
PubMed1996

Cocaine-associated intracranial hemorrhage: absence of vasculitis in 14 cases.

Complications associated with the use of cocaine are varied, and include cerebral hemorrhage and ischemia, with vasculitis and vasospasm as possible etiologies. We reviewed selected brain samples from 14 autopsy cases of cocaine-related cerebrovascular disease. Intracerebral or subarachnoid hemorrhage was present in 12 cases. Intracranial arterioles were either normal or showed nonspecific changes. From these observations, we suggest that intracranial hemorrhages occur in the absence of readily detectable vascular abnormalities.

Adult↗
PubMed1996

Effects of CD11b/18 monoclonal antibody on rats with permanent middle cerebral artery occlusion.

The progression of a lesion from ischemic injury to infarct, after the permanent occlusion of a middle cerebral artery, may be influenced by the influx of leukocytes into the ischemic territory. We aimed to evaluate the effectiveness of treating rats that had permanent middle cerebral artery occlusion with a single dose of an anti-CD11b/18 monoclonal antibody injected 1 hour after the arterial occlusion. To mimic the clinical situation of patients with ischemic strokes who may be treated within 1 hour of the ischemic event, the artery remained occluded. Forty-one adult Wistar rats had permanent middle cerebral artery occlusion, and one was subjected to a sham operation. One hour later, 22 rats received CD11b/18 monoclonal antibody and an additional 20 were injected either with a nonspecific antibody (n = 10) or a buffer solution (n = 10). Experiments were terminated at intervals ranging 12 to 96 hours after the arterial occlusion. Endpoints included neurological testing, daily evaluation of body weight, counts of white blood cells in the peripheral blood, measurement of the area of pallor in the ischemic hemisphere, counts of necrotic neurons, and counts of leukocytes sequestered in the ischemic hemisphere. In experiments terminated 12 hours after the arterial occlusion (n = 4), there were fewer necrotic neurons in the group treated with the CD11b/18 monoclonal antibody compared with the two controls (P < .05), but this difference was not reflected in the neurological scores. Numbers of necrotic neurons in experiments terminated > 12 hours later were not different among the three subgroups. White blood cell counts in peripheral blood were lower in animals with arterial occlusion injected with the monoclonal antibody CD11b/18 (P < .05); numbers of leukocytes sequestered in the ischemic hemisphere were not different in the three groups. Neither changes in body weight nor in the volume of the area of pallor were significantly different among the three groups.

Animals↗
PubMed1996

Carotid atherosclerosis. Definition, pathogenesis, and clinical significance.

Atherosclerotic plaques are aggregates of plasma lipids (especially cholesterol), cells (smooth muscle cells and monocytes/macrophages), and connective tissue matrix (collagen fibers and proteoglycans). Symptomatic plaques in the carotid artery involve primarily the carotid bulb and are characterized by increased cellular proliferation, lipids accumulation, calcification, ulceration, hemorrhage, and thrombosis. Risk factors (arterial hypertension, cigarette smoking, high serum levels of cholesterol, and fibrinogen) promote thrombus formation and continuous transendothelial seepage of plasma lipids.

Arteriosclerosis↗
PubMed1995

Strokes in childhood.

Brain infarcts and brain hemorrhages in patients younger than 20 years are significantly less common than among those older than 65 years; also, their clinical expressions are different from those common to older patients. Congenital defects involving the heart and the arteries supplying the brain are among the most common causes of stroke in the young. In addition to the structural changes affecting the heart and blood vessels, various genetic disorders (hematologic, mitochondrial, and others) are being identified as significant risk factors in an increasing number of young stroke victims.

Adolescent↗