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R Prado

Publications and source records attributed to R Prado.

At least 19 recordsLinked to original sources
PubMed2006

Salt and solvent effects on the kinetics and thermodynamics of the inclusion of the ruthenium complex [Ru(NH3)5(4,4'-bpy)]2+ in beta-cyclodextrin.

The influences of solvents (in water-cosolvent mixtures) and salts on the kinetics and thermodynamics of the inclusion of [Ru(NH3)5(4,4'-bpy)]2+ in beta-cyclodextrin (beta-CD) have been studied. Solvent effects on the kinetics can be described as a consequence of the competition of the cosolvent for the beta-CD cavity. The salt effects on the kinetics depend on the ion pairing of the anions with the [Ru(NH3)5(4,4'-bpy)]2+ complex. On the other hand, the solvent effects on the equilibrium constant depend on the stabilization of the 4,4'-bipyridine ligand in the water-cosolvent mixture relative to water. Finally, salt effects on the equilibrium constant are interpreted as a consequence of ion pairing between the anion of the salt and the inclusion complex.

Kinetics↗
PubMed2004

Studies on medicinal plants of Ivory Coast: investigation of Sida acuta for in vitro antiplasmodial activities and identification of an active constituent.

Sida acuta Burm. (Malvaceae) originating from Ivory Coast was selected after an ethnobotanical survey: traditional healers of malaria commonly used this plant for the treatment. Extracts were tested on two strains of Plasmodium falciparum: FcM29-Cameroon (chloroquine-resistant strain) and a Nigerian chloroquine-sensitive strain. Extracts were obtained by preparing decoction in water of the powdered plant, the technique used by most of the traditional healers. An ethanol extract was then made and tested. The IC50 values obtained for these extracts ranged from 3.9 to -5.4 microg/ml. Purification of this active fraction led to the identification of cryptolepine as the active antiplasmodial constituent of the plant.

Animals↗
PubMed2003

Hyperbaric oxygen therapy protects against mitochondrial dysfunction and delays onset of motor neuron disease in Wobbler mice.

The Wobbler mouse is a model of human motor neuron disease. Recently we reported the impairment of mitochondrial complex IV in Wobbler mouse CNS, including motor cortex and spinal cord. The present study was designed to test the effect of hyperbaric oxygen therapy (HBOT) on (1) mitochondrial functions in young Wobbler mice, and (2) the onset and progression of the disease with aging. HBOT was carried out at 2 atmospheres absolute (2 ATA) oxygen for 1 h/day for 30 days. Control groups consisted of both untreated Wobbler mice and non-diseased Wobbler mice. The rate of respiration for complex IV in mitochondria isolated from motor cortex was improved by 40% (P<0.05) after HBOT. The onset and progression of the disease in the Wobbler mice was studied using litters of pups from proven heterozygous breeding pairs, which were treated from birth with 2 ATA HBOT for 1 h/day 6 days a week for the animals' lifetime. A "blinded" observer examined the onset and progression of the Wobbler phenotype, including walking capabilities ranging from normal walking to jaw walking (unable to use forepaws), and the paw condition (from normal to curled wrists and forelimb fixed to the chest). These data indicate that the onset of disease in untreated Wobbler mice averaged 36+/-4.3 days in terms of walking and 40+/-5.7 days in terms of paw condition. HBOT significantly delayed (P<0.001 for both paw condition and walking) the onset of disease to 59+/-8.2 days (in terms of walking) and 63+/-7.6 days (in terms of paw condition). Our data suggest that HBOT significantly ameliorates mitochondrial dysfunction in the motor cortex and spinal cord and greatly delays the onset of the disease in an animal model of motor neuron disease.

Animals↗
PubMed2002

In vitro antiplasmodial activity of extracts of Alchornea cordifolia and identification of an active constituent: ellagic acid.

Extracts of leaves of Alchornea cordifolia were studied for their antiplasmodial activities. Chloroformic and ether extracts were found to be inactive while the ethanolic extract exhibited mild in vitro activity against Plasmodium falciparum. Fractionation of this extract led us to isolate ellagic acid as the active constituent of the extract with IC(50) in the range of 0.2-0.5 microM. Cytotoxicity of ethanolic fraction and ellagic acid was also estimated on human fibroblasts cells (IC(50) on Hela cells = 7.3 microM at 24 h for ellagic acid).

Animals↗
PubMed2000

EEG effects of ECT: implications for rTMS.

Electroconvulsive therapy (ECT) involves the use of electrical stimulation to elicit a series of generalized tonic-clonic seizures for therapeutic purposes and is the most effective treatment known for major depression. These treatments have significant neurophysiologic effects, many of which are manifest in the electroencephalogram (EEG). The relationship between EEG data and the response to ECT has been studied since the 1940s, but for many years no consistent correlates were found. Recent studies indicate that a number of specific EEG features recorded during the induced seizures (ictal EEG) as well as before and after a course of treatment (interictal EEG) are related to both the therapeutic efficacy and cognitive side effects. Similar to ECT, repetitive transcranial magnetic stimulation (rTMS), which involves focal electromagnetic stimulation of cortical neurons, has also been studied as an antidepressant therapy and also appears to have neurophysiologic effects, although these have not been as fully investigated as is the case with ECT. Given the similarity of these treatments, it is natural to consider whether advances in understanding the electrophysiologic correlates of the ECT response might have implications for rTMS. The present article reviews the literature on the EEG effects of ECT and discusses the implications in terms of the likely efficacy and side effects associated with rTMS in specific anatomic locations, the potential for producing an antidepressant response with rTMS without eliciting seizure activity, eliciting focal seizures with rTMS, and the possibility of using rTMS to focally modulate seizure induction and spread with ECT to optimize treatment.

Brain Mapping↗
PubMed2000

Thromboembolic events lead to cortical spreading depression and expression of c-fos, brain-derived neurotrophic factor, glial fibrillary acidic protein, and heat shock protein 70 mRNA in rats.

The hypotheses that cerebral embolic events lead to repetitive episodes of cortical spreading depression (CSD) and that these propagating waves trigger the expression of c-fos, brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and heat shock protein 70 (HSP70) mRNA were tested. Wistar rats underwent photochemically induced right common carotid artery thrombosis (CCAT) (n = 18) or sham (n = 8) procedures. In a subgroup of rats (n = 5), laser-Doppler flowmetry probes were placed overlying the right parietal cortex to record CSD-like changes in cortical blood flow during the initial 2-hour postinjury period. Rats were killed by decapitation at 2 or 24 hours after CCAT, and brains were processed for in situ localization of the gene expression. Two to five intermittent transient hyperemic episodes lasting 1 to 2 minutes were recorded ipsilaterally after CCAT. At 2 hours after CCAT, the widespread expression of c-fos and BDNF mRNAs was observed throughout the ipsilateral cerebral cortex. Pretreatment with the N-methyl-D-aspartate receptor blocker MK-801 (2 mg/kg) 1 hour before CCAT reduced the expression of BDNF mRNA expression at 2 hours. At 24 hours after CCAT, increased expression of GFAP mRNA was present in cortical and subcortical regions. In contrast, multifocal regions of HSP70 expression scattered throughout the thrombosed hemisphere were apparent at both 2 and 24 hours after injury. These data indicate that thromboembolic events lead to episodes of CSD and time-dependent alterations in gene expression. The ability of embolic processes to induce widespread molecular responses in neurons and glia may be important in the pathogenesis of transient ischemic attacks and may influence the susceptibility of the postembolic brain to subsequent insults including stroke.

Animals↗
PubMed1999

New methods of time series analysis of non-stationary EEG data: eigenstructure decompositions of time varying autoregressions.

OBJECTIVE: Those who analyze EEG data require quantitative techniques that can be validly applied to time series exhibiting ranges of non-stationary behavior. Our objective is to introduce a new analysis technique based on formal non-stationary time series models. This novel method provides a decomposition of the time series into a set of 'latent' components with time-varying frequency content. The identification of these components can lead to practical insights and quantitative comparisons of changes in frequency structure over time in EEG time series. METHODS: The technique begins with the development of time-varying autoregressive models of the EEG time series. Such models have been previously used in EEG analysis but we extend their utility by the introduction of eigenstructure decomposition methods. We review the basis and implementation of this method and report on the analysis of two channel EEG data recorded during 3 generalized tonic-clonic seizures induced in an individual as part of a course of electroconvulsive therapy for major depression. RESULTS: This technique identified EEG patterns consistent with prior reports. In addition, it quantified a decrease in dominant frequency content over the seizures and suggested for the first time that this decrease is continuous across the end of the seizures. The analysis also suggested that the seizure EEG may be best modeled by the combination of multiple processes, whereas post-ictally there appears to be one dominant process. There was also preliminary evidence that these features may differ as a function of ECT therapeutic effectiveness. CONCLUSIONS: Eigenanalysis of time-varying autoregressive models has promise for improving the analysis of EEG time series.

Brain↗
PubMed1999

Delayed hypovolemic hypotension exacerbates the hemodynamic and histopathologic consequences of thromboembolic stroke in rats.

Abnormalities in cerebrovascular reactivity or hemodynamic reserve are risk factors for stroke. The authors determined whether hemodynamic reserve is reduced in an experimental model of thromboembolic stroke. Nonocclusive common carotid artery thrombosis (CCAT) was produced in rats by a rose bengal-mediated photochemical insult, and moderate hypotension (60 mm Hg/30 min) was induced 1 hour later by hemorrhage. Alterations in local cerebral blood flow (ICBF) were assessed immediately after the hypotensive period by 14C-iodoantipyrine autoradiography, and histopathologic outcome was determined 3 days after CCAT. Compared to normotensive CCAT rats (n = 5), induced hypotension after CCAT (n = 7) led to enlarged regions of severe ischemia (i.e., mean ICBF < 0.24 mL/g/min) in the ipsilateral hemisphere. For example, induced hypotension increased the volume of severely ischemic sites from 16 +/- 4 mm3 (mean +/- SD) to 126 +/- 99 mm3 (P < 0.05). Histopathologic data also showed a larger volume of ischemic damage with secondary hypotension (n = 7) compared to normotension (22 +/- 15 mm3 versus 5 +/- 5 mm3, P < .05). Both hypotension-induced decreases in ICBF and ischemic pathology were commonly detected within cortical anterior and posterior borderzone areas and within the ipsilateral striatum and hippocampus. In contrast to CCAT, mechanical ligation of the common carotid artery plus hypotension (n = 8) did not produce significant histopathologic damage. Nonocclusive CCAT with secondary hypotension therefore predisposes the post-thrombotic brain to hemodynamic stress and structural damage.

Animals↗
PubMed1999

Thromboembolic events predispose the brain to widespread cerebral infarction after delayed transient global ischemia in rats.

BACKGROUND AND PURPOSE: Transient distal platelet accumulation after common carotid artery thrombosis (CCAT) leads to hemodynamic, metabolic, and molecular events that may influence the response of the postthrombotic brain to secondary insults. We investigated how a thromboembolic insult would affect histopathological outcome when combined with an ischemic insult induced 24 hours later. METHODS: Three groups of rats underwent either (1) CCAT+10 minutes of normothermic 2-vessel occlusion (n=6), (2) CCAT+sham ischemia procedures (n=6), or (3) sham CCAT procedures+10 minutes of 2-vessel occlusion (n=6). At 7 days, rats were perfused for quantitative histopathological and immunocytochemical analysis. RESULTS: Rats undergoing combined insults (group 1) had significantly larger areas of ischemic injury (P<0.05) within the cerebral cortex, striatum, and thalamus compared with the other, single-injury groups. Increased ischemic damage included selective neuronal necrosis, infarction, and focal hemorrhage. By means of glial fibrillary acidic protein immunocytochemistry and lectin histochemistry, reactive astrocytes and microglia were found to be associated with widespread tissue necrosis. In contrast, infrequent infarction or CA1 hippocampal neuronal necrosis was observed in groups 2 and 3, respectively. CONCLUSIONS: A prior thromboembolic event is a risk factor for widespread cerebral infarction and hemorrhage when combined with a delayed ischemic insult. The understanding of what factors enhance the susceptibility of the postthrombotic brain to secondary insults may aid in the development of neuroprotective strategies to be applied after transient ischemic attacks to prevent the initiation of stroke.

Animals↗
PubMed1998

White matter alterations following thromboembolic stroke: a beta-amyloid precursor protein immunocytochemical study in rats.

Thromboembolic stroke in rats leads to a well-described pattern of histopathological and behavioral abnormalities. However, limited data are available in animal models concerning the response of the white matter to embolic events. The purpose of this study was to document patterns of white matter abnormalities using beta-amyloid precursor protein (betaAPP) immunocytochemistry as a marker of axonal damage. Twelve male Wistar rats underwent photochemically induced right common carotid artery thrombosis (CCAT) or sham procedures. At 3 days after CCAT, rats were perfusion-fixed and sections immunostained for the visualization of betaAPP or stained with hematoxylin and eosin for routine histopathological analysis. As previously described, CCAT produced small ipsilateral embolic infarcts and ischemic cell change within gray matter structures including the medial cerebral cortex, striatum, hippocampus and thalamus. In areas of frank infarction, numerous reactive profiles were observed within borderzones of the damaged site. However, betaAPP immunocytochemistry also revealed reactive axonal profiles within various white matter tracts including the corpus callosum, external capsule and fimbria of the hippocampus. In many cases, the presence of axonal damage could not be appreciated with routine hematoxylin and eosin staining. These data indicate that CCAT leading to platelet embolization to the brain not only produces embolic infarcts but also produces more subtle white matter abnormalities. Previously undetected white matter damage would be expected to participate in the sensorimotor and cognitive behavioral deficits following embolic stroke.

Amyloid beta-Protein Precursor↗
PubMed1998

Ritanserin, a 5-HT2 receptor antagonist, increases subcortical blood flow following photothrombotic middle cerebral artery occlusion in rats.

It has been proposed that the reversal of serotonin-mediated vasoconstriction accounts for the neuroprotective effect of serotonin (5-HT2) receptor blockade in focal cerebral ischemia. We investigated the effect of pretreatment with ritanserin, a 5-HT2 receptor antagonist, on cerebral blood flow in a model of photothrombotic middle cerebral artery occlusion in rats. Local cerebral blood flow was measured by iodoantipyrine autoradiography 30 minutes after induction of ischemia. Using a novel image-alignment algorithm, 3-dimensional reconstructions of averaged cerebral blood flow were calculated. The difference-image of local cerebral blood flow between ritanserin and vehicle-treated animals revealed a subcortical zone underlying the ischemic cortex where cerebral blood flow was markedly enhanced indicating a beneficial hemodynamic effect of ritanserin. Three-dimensional image analysis provides a powerful tool to detect inter-group differences of cerebral blood flow which are underestimated by conventional types of data analysis.

Animals↗
PubMed1998

Posttraumatic cerebral ischemia after fluid percussion brain injury: an autoradiographic and histopathological study in rats.

OBJECTIVES: Mild-to-moderate reductions in local cerebral blood flow (ICBF) have been reported to occur in rats after moderate (1.7-2.2 atm) fluid percussion brain injury. The purpose of this study was to determine whether evidence for severe ischemia (i.e., mean ICBF < 0.25 ml/g/min) could be demonstrated after severe brain injury. In addition, patterns of indium-labeled platelet accumulation and histopathological outcome were correlated with the hemodynamic alterations. METHODS: Sprague-Dawley rats (n = 23), anesthetized with halothane and maintained on a 70:30 mixture of nitrous oxide:oxygen and 0.5% halothane, underwent normothermic (37 degrees C) parasagittal fluid percussion brain injury (2.4-2.6 atm). Indium-111-tropolone-labeled platelets were injected 30 minutes before traumatic brain injury (TBI), while 14C-iodoantipyrine was infused 30 minutes after trauma for ICBF determination. Sham-operated animals (n = 8) underwent similar surgical procedures but were not injured. For histopathological analysis, traumatized rats (n = 5) were perfusion-fixed 3 days after TBI. RESULTS: In autoradiographic images of indium-labeled platelets, abnormal platelet accumulation that was most pronounced overlying the pial surface was commonly associated with severe reductions in ICBF within underlying cortical regions 30 minutes after TBI. For example, within the lateral parietal cortex, ICBF was significantly reduced from 1.67 +/- 0.11 ml/g per minute (mean +/- standard error of the mean) in sham-operated animals to 0.23 +/- 0.03 ml/g per minute within the traumatized group. In addition to focal severe ischemia, moderate reductions in ICBF were detected throughout the traumatized hemisphere, including the frontal and occipital cortices, hippocampus, thalamus, and striatum. Mild decreases in ICBF were also observed throughout the contralateral cerebral cortex. At 3 days after severe TBI, histopathology demonstrated intracerebral and subarachnoid hemorrhage associated with cerebral contusion and selective neuronal necrosis. CONCLUSION: These data indicate that multiple cerebrovascular abnormalities, including subarachnoid hemorrhage, focal platelet accumulation, and severe ischemia, are important early events in the pathogenesis of cortical contusion formation after TBI. Injury severity is expected to be a critical factor in determining what therapeutic strategies are attempted in the clinical setting.

Animals↗
PubMed1997

The role of nitric oxide in the pathophysiology of thromboembolic stroke in the rat.

Although nitric oxide (NO) has been shown to play an important role in the pathophysiology of cerebral ischemia, its contribution to the pathogenesis of experimentally induced thromboembolic stroke is unknown. In this study, we pharmacologically manipulated NO levels in the acute post-thrombotic stage and determined the effects on behavior and histopathology. The following drugs were used: nitro-L-arginine-methyl ester (L-NAME), a non-specific endothelial and neuronal nitric oxide synthase (eNOS and nNOS) inhibitor, 3-bromo-7-nitroindazole (7-NI), a specific inhibitor for nNOS, the NO precursor, exogenous L-arginine and the NO-donor, 3-morpholino-sydnonimine (SIN-1). Male Wistar rats (n = 76) were randomly assigned to receive vehicle or drug immediately after common carotid artery thrombosis (CCAT). Regional measurements of cortical NOS activity using the [3H]L-arginine to [3H]L-citrulline conversion assay were decreased 1 h after treatment with L-NAME and 7-NI by 50 and 65%, respectively; hippocampal NOS activity was reduced with L-NAME by 35% and with 7-NI by 65%. L-NAME significantly worsened forelimb placing as compared to other groups. 7-NI accelerated sensorimotor recovery. Water maze retention deficits were noted 48 h after CCAT and these were exacerbated by L-NAME treatment. Histopathological protection was conferred in the hippocampus by 7-NI and SIN-1; conversely, L-NAME increased neuronal injury in the contralateral cortex. L-arginine had no effect on these outcomes. In conclusion, both structural and functional consequences of CCAT can be aggravated by limiting endothelial NO production in the acutely post-thrombotic brain. In contrast, inhibition of nNOS and infusion of an NO donor has a beneficial effect on pathology.

Animals↗
PubMed1997

The effect of nitric oxide synthase inhibition on acute platelet accumulation and hemodynamic depression in a rat model of thromboembolic stroke.

The relative importance of hemodynamic factors in the pathogenesis of thrombotic or embolic stroke is unclear. Of particular therapeutic interest are those substances that facilitate vasodilation and the clearance of platelet aggregates in the compromised microvasculature. A likely contributor to these functions is nitric oxide because it is known to inhibit platelet aggregability and promote vascular relaxation. To investigate the involvement of nitric oxide in the hemodynamic changes after experimental ischemia, photochemically induced nonocclusive common carotid artery thrombosis (CCAT) was studied. CCAT is a rat model of unilateral carotid artery stenosis and platelet embolization to the brain. This study characterized the acute hemodynamic consequences of CCAT and the resultant pattern of platelet deposits with and without nitric oxide synthase inhibition by nitro-L-arginine methyl ester (L-NAME). In addition, the subacute local cerebral blood flow changes were studied at 24 hours. Right CCAT was produced in 30 male Wistar rats injected with (111)In-labeled platelets. Between 5 and 15 minutes after thrombosis, rats were treated with either 15 mg/kg of L-NAME (intravenously) or saline vehicle. Hemodynamic changes were studied 30 to 45 minutes after thrombosis using [14C]iodoantipyrine autoradiography. Eight coronal levels were analyzed, and cortical and subcortical regions of interest were defined. Significant increases were observed in total platelets in the ipsilateral hemisphere after L-NAME treatment, and in the distribution of platelets in the anterior frontal and occipital cortices with nitric oxide synthase inhibition, encompassing the anterior and posterior border zone areas of the ipsilateral cortex. Otherwise, foci of labeled platelets were detected throughout the ipsilateral and contralateral hemispheres. Mean local cerebral blood flow images (n = 5) revealed a moderate bilateral global reduction in flow acutely, which normalized in the untreated thrombosed group by 24 hours. In contrast, the L-NAME-treated groups (sham and experimental) had lasting, widespread reductions in flow of approximately 25%. Pairwise comparisons between groups showed that CCAT/L-NAME was significantly different from shams in the corpus callosum and different from L-NAME shams in the internal capsule (P < 0.05) These hemodynamic and platelet accumulation changes may partially account for the aggravation of cognitive and sensorimotor deficits previously reported in this model of thromboembolic stroke.

Animals↗
PubMed1996

Widespread hemodynamic depression and focal platelet accumulation after fluid percussion brain injury: a double-label autoradiographic study in rats.

Cerebrovascular damage leading to subsequent reductions in local cerebral blood flow (lCBF) may represent an important secondary injury mechanism following traumatic brain injury (TBI). We determined whether patterns of 111-indium-labeled platelet accumulation were spatially related to alterations in lCBF determined autoradiographically 30 min after TBI. Sprague-Dawley rats (n = 8), anesthetized with halothane and maintained on a 70:30 (vol/vol) mixture of nitrous oxide/oxygen and 0.5% halothane, underwent parasagittal fluid percussion brain injury (1.7-2.2 atm). 111-Indium-tropolone-labeled platelets were injected 30 min prior to TBI while [14C]-iodoantipyrine was infused 30 min after trauma. Sham-operated animals (n = 7) underwent similar surgical procedures but were not injured. In autoradiographic images of the indium-labeled platelets, focal sites of platelet accumulation within the traumatized hemisphere were restricted to the pial surface (five of eight rats), the external capsule underlying the lateral parietal cortex (five of eight rats), and within cerebrospinal fluid (CSF) compartments (six of eight rats). In contrast, mild-to-moderate reductions in lCBF, not restricted to sites of platelet accumulation, were seen throughout the traumatized hemisphere. Flow reductions were most severe in coronal sections underlying the impact site. For example, within the lateral parietal cortex and hippocampus, lCBF was significantly reduced [p <0.01; analysis of variance (ANOVA)] from 1.71 +/- 0.34 (mean +/- SD) and 0.78 +/- 0.12 ml/g/min, respectively, versus 0.72 +/- 0.17 and 0.41 +/- 0.06 ml/g/min within the traumatized hemisphere. Significant flow reductions were also seen in remote cortical and subcortical areas, including the right frontal cortex and striatum. These results indicate that focal platelet accumulation and widespread hemodynamic depression are both early consequences of TBI. Therapeutic strategies directed at these early microvascular consequences of TBI may be neuroprotective by attenuating secondary ischemic processes.

Animals↗
PubMed1996

L-arginine does not improve cortical perfusion or histopathological outcome in spontaneously hypertensive rats subjected to distal middle cerebral artery photothrombotic occlusion.

The potential of nitric oxide (NO) to influence positively or negatively the outcome of mechanically induced focal cerebral ischemia is still controversial. Recent evidence suggests that NO of vascular origin, whether synthesized from exogenously administered L-arginine (L-Arg) or from NO donor compounds, is beneficial but that of neuronal origin is not. However, the therapeutic potential of NO to ameliorate stroke induced by arterial thrombosis has not been reported. We assessed the therapeutic effect of L-Arg administration in spontaneously hypertensive rats (SHR) subjected to permanent photothrombotic occlusion of the distal middle cerebral artery (dMCA). The ipsilateral carotid artery was left unligated to enhance L-Arg delivery into the putative penumbral region. Local CBF (LCBF) was assessed at 30 min by the [14C]iodoantipyrine technique (n = 9), while histological infarct volumes and index of peripheral ischemic cell change were determined at 3 days (n = 7). Rats (n = 9) given 300 mg/kg L-Arg at 18 and 3 h before photothrombotic dMCA occlusion and at 5 min afterward displayed no significant differences in LCBF compared with animals (n = 8) injected with water (the carrier vehicle) and similarly irradiated. Infarct volumes were also similar, being 37.0 +/- 9.7 mm3 (SD) in the vehicle-treated and 49.1 +/- 17.2 mm3 (SD) in the L-Arg-treated groups (both n = 7), as were assessments of ischemic neuronal density in the penumbra. In contrast, L-Arg administered intravenously in a dose of 300 mg/kg to nonischemic SHR (n = 5) increased cortical CBF by approximately 75% during a 70-min observation period. We conclude that thrombotic processes superimposed upon cerebral ischemia may facilitate tissue reactions that offset the potentially beneficial effect of L-Arg, and this caveat must be considered when proposing L-Arg for clinical treatment of focal thrombotic stroke.

Animals↗
PubMed1996

Depiction of infarct frequency distribution by computer-assisted image mapping in rat brains with middle cerebral artery occlusion. Comparison of photothrombotic and intraluminal suture models.

BACKGROUND AND PURPOSE: Histopathologic analysis of experimental brain damage has traditionally been performed by measuring areas of infarction and/or selective neuronal alterations on a section-by-section basis in individual animals. For series containing multiple replicate animals, quantitation of tissue injury is typically performed at similar coronal levels throughout an experimental group. A means of facilitating pictorial group comparisons of these histopathologic alterations between different series of replicate studies is highly desirable. METHODS: We introduce a newly designed approach to achieve this goal, based on a linear affine transformation that is used to map corresponding sections at the same anatomic level into a common template to yield a frequency distribution map depicting the aggregate data set. We have applied this approach to compare the histopathologic features of two models of middle cerebral artery (MCA) occlusion in rats: (1) photothrombotically induced permanent distal MCA occlusion in spontaneously hypertensive rats (SHR) and (2) temporary MCA occlusion by intraluminal suture in Wistar rats. RESULTS: The brains of SHR rats with permanent distal MCA occlusion showed a high frequency of infarction involving the dorsolateral and lateral portions of the ipsilateral neocortex, whereas Wistar rats with 90-minute MCA suture occlusion showed a zone of infarction largely concentrated in the dorsolateral portion of the ipsilateral caudoputamen. Infarct frequency distributions for the two animal groups were compared statistically at three corresponding anatomic levels by Fisher's exact test; the resulting statistical parametric maps are shown. CONCLUSIONS: With the use of frequency distribution maps, the pattern of trends within a group can be observed coronally or three-dimensionally. One can directly access data as to numbers of rats with infarction for any point on the map. Studies performed under different experimental conditions can also be compared with one another by means of the generated data sets.

Animals↗