Biomedical subjects

Fernando G Diaz

Publications and source records attributed to Fernando G Diaz.

At least 19 recordsLinked to original sources

PubMed2005

Postischemic reperfusion: ultrastructural blood-brain barrier and hemodynamic correlative changes in an awake model of transient forebrain ischemia.

OBJECTIVE: In nonrecovery models of cerebral ischemia, blood-brain barrier (BBB) and cerebral blood flow (CBF) changes are known to occur during reperfusion. It is unknown, however, whether those CBF and BBB alterations occur after brief, transient ischemia with neurological recovery. The purpose of this study was to characterize the time course of CBF and BBB ultrastructural changes during reperfusion in an awake, recovery model of transient global forebrain ischemia (GFI). METHODS: Forty-five adult Sprague-Dawley rats were subjected, while awake, to 10 minutes of GFI by the nine-vessel occlusion method. Thirty-five age-matched animals composed a sham-operated group. Normal control (n = 5), sham-operated (n = 5), and nine-vessel occlusion/reperfusion (n = 15) rats were selected for ultrastructural analysis. Electroencephalography was performed, and CBF, mean arterial blood pressure, and intracranial pressure were measured during ischemia and reperfusion up to 24 hours. Quantitative morphological analysis of cortical BBB capillaries was performed by transmission electron microscopy at the same time points at which specific CBF changes occurred during reperfusion. RESULTS: CBF decreased to 6% of preocclusion values during GFI. This correlated with coma and decerebrate rigidity. During reperfusion, short-lived hyperemia (225 +/- 18%, P < 0.001) was characterized by increased intracranial pressure (28.3 +/- 2.6 mm Hg, P < 0.001) and isoelectric electroencephalogram. This was followed by hypoperfusion, which reached a nadir of 59.7% (59.7 +/- 8.8%, P < 0.01) from baseline by 90 minutes. At this time point, the electroencephalogram recovered, and intracranial pressure and mean arterial blood pressure showed no abnormalities. By 8.5 hours, CBF returned to normal, and this coincided with complete recovery of the animal. Ultrastructural BBB analysis revealed astrocyte end-foot process edema and patent capillaries during hyperemia. Severe interstitial BBB edema and capillary lumen collapse was observed during hypoperfusion. Detachment and migration of pericytes was observed during hypoperfusion and beyond. CONCLUSION: A biphasic CBF response is elicited during reperfusion after brief nonlethal GFI under awake conditions.

Animals↗

PubMed2004

Long-term neuroprotection induced by regional brain cooling with saline infusion into ischemic territory in rats: a behavioral analysis.

The neuroprotective effect of hypothermia has long been recognized. Our recent studies have demonstrated the significant therapeutic value of local brain cooling in the ischemic territory prior to reperfusion in stroke, with reduced infarction and inflammatory responses up to 48 hours of reperfusion. The goal of this study was to determine if local brain cooling, produced by infusion of cold saline, could induce long-term functional improvement after stroke. A hollow filament was used to block the middle cerebral artery (MCA) for 3 hours, and then to locally infuse the ischemic territory with 6 ml cold saline (20 degrees C) for 10 minutes prior to reperfusion. This brain cooling infusion induced a significant (p < 0.01) decrease in neurologic deficits and significantly (p < 0.01) improved motor behavior in ischemic rats after 14 days of reperfusion, compared with ischemic rats without local cold saline infusion. This improvement continued for up to 28 days after reperfusion. No significant difference in motor performance was observed between the brain cooling infusion and normal control groups. Significant (p < 0.01) reductions in infarct volume were also evident. In conclusion, a local cerebral hypothermia induced by local saline infusion prior to reperfusion produced a long-term functional recovery after ischemic stroke. A therapeutic procedure, which combines prereperfusion infusion into an ischemic region with coincident cerebral hypothermia and perhaps subsequent recanalization of an occluded intracranial vessel, may improve the outcome for stroke patients.

Animals↗

PubMed2004

Local saline infusion into ischemic territory induces regional brain cooling and neuroprotection in rats with transient middle cerebral artery occlusion.

OBJECTIVE: The neuroprotective effect of hypothermia has long been recognized. Use of hypothermia for stroke therapy, which is currently being induced by whole-body surface cooling, has been limited primarily because of management problems and severe side effects (e.g., pneumonia). The goal of this study was to determine whether local infusion of saline into ischemic territory could induce regional brain cooling and neuroprotection. METHODS: A novel procedure was used to block the middle cerebral artery of rats for 3 hours with a hollow filament and locally infuse the middle cerebral artery-supplied territory with 6 ml cold saline (20 degrees C) for 10 minutes before reperfusion. RESULTS: The cold saline infusion rapidly and significantly reduced temperature in cerebral cortex from 37.2 +/- 0.1 to 33.4 +/- 0.4 degrees C and in striatum from 37.5 +/- 0.2 to 33.9 +/- 0.4 degrees C. The significant hypothermia remained for up to 60 minutes after reperfusion. Significant (P < 0.01) reductions in infarct volume (approximately 90%) were evident after 48 hours of reperfusion. In ischemic rats that received the same amount of cold saline systemically through a femoral artery, a mild hypothermia was induced only in the cerebral cortex (35.3 +/- 0.2 degrees C) and returned to normal within 5 minutes. No significant reductions in infarct volume were observed in this group or in the ischemic group with local warm saline infusion or without infusion. Furthermore, brain-cooling infusion significantly (P < 0.01) improved motor behavior in ischemic rats after 14 days of reperfusion. This improvement continued for up to 28 days after reperfusion. CONCLUSION: Local prereperfusion infusion effectively induced hypothermia and ameliorated brain injury from stroke. Clinically, this procedure could be used in acute stroke treatment, possibly in combination with intra-arterial thrombolysis or mechanical disruption of clot by means of a microcatheter.

Animals↗

PubMed2004

Exercise-induced overexpression of angiogenic factors and reduction of ischemia/reperfusion injury in stroke.

The purpose of this study was to determine if exercise could induce expression of vascular endothelial growth factor (VEGF) and angiopoietin 1 and 2, in association with angiogenesis; and if angiogenic changes correlated with reduced brain injury in stroke. Adult male Sprague Dawley rats (3 month old, n=44) were exercised on a treadmill 30 minutes each day for 1, 3 or 6 weeks, or housed as non-exercised controls for 3 weeks. Some 3 week-exercised rats were then housed for an additional 3 weeks. Exercise significantly (p<0.01) increased mRNA (determined by real-time reverse transcriptase-polymerase chain reaction) expression of angiopoietin 1 and 2 as early as 1 week, with further increases occurring at 3 weeks. A mild increase after 1 week and a robust increase after 3 weeks of exercise in four isoforms (120, 144, 164, 188) of VEGF mRNA levels were significantly (p<0.01) observed, with VEGF(144) being more markedly up-regulated. Overexpression of the mRNAs decreased upon withdrawal of exercise. A significant increase (p<0.01) in the density of microvessels (determined by laminin-immunocytochemistry) was found at 3 weeks of exercise and this continued after exercise was withdrawn. In exercising rats subjected to 2-h MCA occlusion followed by 48-h reperfusion, neurological deficits and infarct volume were significantly reduced. Neuroprotection continued after 3 weeks of rest. This study indicates that pre-ischemic exercise reduces brain injury in stroke. The reduced damage is associated with angiogenesis, possibly induced by angiogenic factors following exercise. Physical exercise up-regulates mRNA levels of the angiopoietin family and VEGF.

Analysis of Variance↗

PubMed2003

Reduced inflammatory mediator expression by pre-reperfusion infusion into ischemic territory in rats: a real-time polymerase chain reaction analysis.

The aim in this study was to investigate if our new experimental model for stroke therapy, flushing the ischemic territory with saline prior to reperfusion, could reduce overexpression of inflammatory mediators during reperfusion. Stroke in Sprague-Dawley rats (n=24) was induced by a 2-h middle cerebral artery occlusion using a novel intraluminal hollow filament. Prior to reperfusion, 12 of the ischemic rats received 6 ml isotonic saline at 37 degrees C infused into the ischemic area through the filament. Expression of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule 1 (ICAM-1) mRNA was analyzed by real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR). A significant overexpression (9-26 fold) of the genes encoding TNF-alpha, IL-1beta and ICAM-1 in ischemic rats was found during early reperfusion without flushing at 6 and 12 h. This increase was significantly reduced at both 6 and 12 h post-reperfusion as a result of saline flushing.

Animals↗

PubMed2003

Regional brain cooling induced by vascular saline infusion into ischemic territory reduces brain inflammation in stroke.

The neuroprotective effect of hypothermia has long been recognized. Use of hypothermia for stroke therapy, which is currently being induced by whole body surface cooling, has been largely limited because of management problems and severe side effects (i.e., pneumonia). Our recent studies have demonstrated the significant therapeutic value of local brain cooling in the ischemic territory prior to reperfusion in stroke. The goal of this study was to determine if cerebral local cooling infusion could reduce stroke-mediated brain injury by inhibiting inflammatory responses. A hollow filament was used to block the middle cerebral artery (MCA) for 3 hours, and then to locally infuse the ischemic territory with 6 ml cold saline (20 degrees C) for 10 min prior to 48-h reperfusion. This cold saline infusion significantly ( P<0.01) reduced temperature of the MCA supplied territory (in cerebral cortex from 37.2+/-0.1 degrees C to 33.4+/-0.4 degrees C, in striatum from 37.5+/-0.2 degrees C to 33.9+/-0.4 degrees C), with the hypothermia remaining for at least 45 min after reperfusion. Consequently, significant ( P<0.01) reductions in endothelial expression of intracellular adhesion molecule-1 (ICAM-1), the key step for inflammatory progress, as well as leukocyte infiltration, were evident in both cortex and striatum after reperfusion. As a control, ischemic rats received the same amount of cold saline systemically through a femoral artery. A mild hypothermia was induced in the cerebral cortex (35.3+/-0.2 degrees C) but not in the striatum (36.8+/-0.2 degrees C). The reduced cortical temperature returned to normal within 5 min. Brain temperature in ischemic rats perfused locally with saline at 37 degrees C remained normal. Intensive expression of ICAM-1 and accumulation of leukocytes was observed in ischemic control groups without brain cooling infusion. In conclusion, brain hypothermia induced by local pre-reperfusion infusion ameliorated brain inflammation from stroke.

Analysis of Variance↗

PubMed2003

Free fatty acids in cerebrospinal fluids from patients with traumatic brain injury.

Free fatty acid (FFA) concentrations in cerebrospinal fluid (CSF) are recognized as markers of brain damage in animal studies. There is, however, relatively little information regarding FFA concentrations in human CSF in normal and pathological conditions. The present study examined FFA concentrations in CSF from 15 patients with traumatic brain injury (TBI) and compared the data with values obtained from 73 contemporary controls. Concentrations of specific FFAs from TBI patients, obtained within 48 h of the insult were significantly greater than those in the control group (arachidonic, docosahexaenoic and myristic, P<0.001; oleic, palmitic, P<0.01; linoleic, P<0.05). Higher concentrations of total polyunsaturated fatty acids (P<0.001) and of arachidonic, myristic and palmitic acids measured individually in CSF (P<0.01) obtained 1 week after the insult were associated with a worse outcome at the time of hospital discharge using the Glasgow Outcome Scale. This preliminary investigation suggests that CSF FFA concentrations may be useful as a predictive marker of outcome following TBI.

Arachidonic Acid↗

PubMed2003

Paraclinoid Carotid Aneurysms: Surgical Management, Complications, and Outcome Based on a New Classification Scheme.

The site of origin, projection, and relationship of aneurysms arising from the ophthalmic segment of the internal carotid artery (ICA) to adjacent structures are heterogeneous. Based on a retrospective analysis of 61 patients with aneurysms in this location, we developed a simple numerical classification system to guide surgical planning. We used angiographic findings to categorize the aneurysms. We followed the nomenclature of the carotid segments by Bouthillier et al (Neurosurgery 1996;38:425-432), C4 being the intracavernous ICA, C5 the clinoidal segment, and C6 the ophthalmic segment of the ICA. The aneurysms were divided into four major types: Types Ia and Ib projected superiorly and arose from the dorsal surface of C6. Type Ia was related to the ophthalmic artery. Type Ib aneurysms were sessile and had no branch relations. Type II aneurysms were related to the ventral wall of the C6 segment without any branch relation. Type IIIa variant arose from medial wall of the C6 segment and was related to the superior hypophyseal artery. Type IIIb arose from the medial wall of the C5 segment below the dural reflection without any branch relation. Large type IV aneurysms arose from the C5 and C6 segments, widening the distal dural ring. Patients' postoperative status and visual and overall outcomes were analyzed. Ultimately, this classification helped us to plan operative approaches and clip selection.

Journal Article↗

PubMed2003

Synaptic plasticity in thalamic nuclei enhanced by motor skill training in rat with transient middle cerebral artery occlusion.

The goal of this study was to determine if synaptic plasticity in the thalamus of rats subjected to stroke could be altered by motor training. Transient occlusion of right middle cerebral artery in adult female Sprague-Dawley rats (n = 35) was induced with an intraluminal filament followed by three training conditions, 1. motor skill training on Rota-rod requiring balance and coordination skills, 2. simple exercise on treadmill, and 3. nontrained controls. Synaptic plasticity in brain was evaluated by synapotophysin immunocytochemistry at 14 or 28 days after training procedures. Infarct volume was determined in Nissl stained sections. Both at 14 and 28 days after Rota-rod training, intense synaptophysin immunoreactivity was present in the right but not the left mediodorsal and ventromedial nuclei of thalamus of ischemic rats. In treadmill-trained animals, however, similarly intense synaptic plasticity in these two thalamic nuclei was seen only at 28 days. Immunostaining was found also in other brain regions adjacent to or remote from infarct site. The data suggest that motor training, particularly motor skill training involving balance and coordination, facilitates a uniquely lateralized synaptogenesis in the thalamus.

Animals↗

PubMed2003

Stereolithography: neurosurgical and medical implications.

We present material to define and understand the concept of Stereolithography (STL) and its potential benefits to the field of neurosurgery and other medical specialties. A historical and scientific review of the literature on stereolithography, its evolution and uses in neurosurgery, forensic medicine, and other medical specialties are described. Considerations regarding different techniques used to obtain STL are discussed. The reproduction of cranial and vascular structures using this technique is evaluated. Data acquisition and model fabrication are the two basic steps required for stereolithography to create custom models for multiple applications in cranio-facial surgery, vascular studies, orthopedic surgery, urology and forensic medicine, among others. Stereolithography is a relatively new technique which continues to grow in many medical fields. Pre-operative education of patients, better understanding of patient anatomy, and the creation of custom-made prostheses are proven benefits of this technique.

Blood Vessels↗

PubMed2003

Advances in ICP monitoring techniques.

With the advent of newer devices for measuring intracranial pressure (ICP) and cerebral metabolism, more alternatives continue to rise aiming to control ICP. This manuscript presents a proposed analysis of different ICP monitoring devices in order to make appropriate selection of them in our clinical setting including general and pediatric applications. A systematic review of the literature was made analyzing the technical advances in ICP monitoring. The recent in vitro and in vivo tests as well as mathematical/computer models were reviewed. Practical applications of principles were discussed and compared based on the mode of pressure transformation. A ventricular catheter connected to an external strain gauge transducer or catheter tip pressure transducer device is considered to be the most accurate method of monitoring ICP and enables therapeutic CSF drainage. The significant infections or hemorrhage associated with ICP devices causing patients morbidity are clinically rare and should not deter the decision to monitor ICP. Parenchymal catheter tip pressure transducer devices are advantageous when ventricular ICP cannot be obtained or if there is an obstruction in the fluid couple, though they have the potential for significant measurement differences and drift due to the inability to recalibrate. Subarachnoid or subdural fluid-coupled devices and epidural ICP devices are currently less accurate. With an increasing miniaturization of the transducers, fiberoptic systems have been developed, however, there is a problem of measurement accuracy during the period of patient monitoring and external calibration should be performed frequently to ensure constant accuracy. Ventriculostomies continue to have a pivotal role in ICP control. With a rational understanding of the applications and limitations of the different ICP monitoring devices, the outcome for critically ill neurological patients is optimized.

Animals↗

PubMed2003

Brain retraction injury.

This paper reviews the literature of the brain retraction injury during the last century. The review focused on the instrument characteristic as well as the physiopathological and histopathological damage of the brain induced by brain retraction. It was found that lesions were induced by cerebral ischemia. We conclude that a better monitoring system needs to be developed to avoid brain injury.

Animals↗

PubMed2002

Late outcome following central nervous system injury in child abuse.

OBJECTIVE: The object of this study was to increase our understanding of the social, clinical, radiographic and psychological consequences of child abuse after the initial insult and to describe the role of neurosurgery and other specialties in this context. METHODS: A review of the literature on child abuse (using scientific journals, textbooks, and internet reports) was conducted, with special attention given to child abuse in infants. The biomechanical patterns of injury, the long-term neurological, psychological, and social outcomes and methods of rehabilitation are reviewed. CONCLUSIONS: Head injury associated with physical abuse carries a significantly worse clinical outcome than accidental trauma. Late findings in CT scans and MRI show evidence of cerebral atrophy in 100% and cerebral ischemia in 50% of physical abuse cases. Abuse and neglect have a strong impact in developing children, producing emotional, cognitive, and social problems that may persist throughout the rest of their lives. Outcome cannot be improved without an integrated rehabilitation strategy encompassing early field management, hospital therapy, precise targeting of educational and cognitive needs, and finally return to the community. New ancillary tests have emerged that are aimed at improving rehabilitation and illuminating the long-term physiological and functional impact of abuse.

Central Nervous System Diseases↗

PubMed2002

Impaired motor activity and motor learning function in rat with middle cerebral artery occlusion.

The poor quality of life after a stroke is largely attributed to deficits in cognitive-motor functioning. The goals of this study were to detect if damaged motor learning function were attributed to motor deficits in rats following a transient middle cerebral artery (MCA) occlusion. Stroke was induced by a 2-h occlusion of the MCA using an intraluminal filament. Motor functions were evaluated from 5 up to 28 days after reperfusion in ischemic and control rats. Motor function was detected by a series of motor tests (runway traversing and beam balancing, as well as foot fault placing, parallel bar crossing, rope and ladder climbing), and motor learning behavior was determined by analyzing the rate of improvement of impaired function during performance of the motor tasks. Significant (P<0.001) motor deficits were detected in the stroke group (n=10) while performing motor tasks that involve extensive coordination, in comparison to the controls (n=12). Although motor behavior was improved with repeated behavior testing, unparalleled rate of improvement of motor performance on rope and ladder climbing tests was found between the two groups, suggesting an impaired motor learning function. Brain tissue damage was detected in the ischemic animals 28 days after surgery, demonstrated by 40% infarct volume of contralateral hemisphere. Both motor learning and motor function were impaired in ischemic rats. The motor tests used in this study are sensitive, semi-quantitative, and reproducible measurements of functional impairment in rats following an ischemic stroke.

Animals↗

PubMed2002

Inhibition of mitochondrial Na(+)/Ca(2+) exchange by 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one attenuates free fatty acid efflux in rat cerebral cortex during ischemia-reperfusion injury.

We evaluated the effects of 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP-37157) (50 muM), a specific inhibitor of mitochondrial Na(+)/Ca(2+) exchange, applied topically onto rat cerebral cortex during ischemia-reperfusion injury. Free fatty acid (FFA) levels in cortical superfusates, withdrawn at 10 min intervals from bilateral cortical windows, were analyzed by high performance liquid chromatography. During a 20 min period of ischemia in control animals, there were significant increases in all FFAs. Following reperfusion, FFA levels remained significantly elevated. Application of CGP-37157 significantly inhibited effluxes of all FFAs during both ischemia and reperfusion. These data indicate that inhibition of mitochondrial Na(+)/Ca(2+) exchange likely prevented the activation of phospholipases that usually occurs following an ischemic insult as evidenced by its attenuation of FFA efflux.

Animals↗

PubMed2002

Intradural invasion of chordoma: two case reports.

Chordomas are rare tumors of the central nervous system and primarily occur in the extradural space. We report two patients with intracranial chordomas located in the region of the clivus that invaded the prepontine cisterns. The patients, 45 and 62 years old, had histories of cranial neuropathies and headache, respectively. Petrosal approaches were performed in both with radical resection of the tumors. Anatomopathological studies confirmed the diagnosis of chordoma. The symptoms of both patients resolved, and they have had no recurrence after 18 months of follow-up. Intradural chordomas or extradural chordomas that invade the intradural space are difficult to differentiate from ecchordoses physaliphorae, a non-neoplastic entity with similar radiological features. MBI-1 studies were therefore performed to confirm the diagnosis of chordoma. The differential diagnosis for these two entities, the different modalities of treatment, and prognosis are reviewed.

Case Reports↗

PubMed2002

Prereperfusion saline infusion into ischemic territory reduces inflammatory injury after transient middle cerebral artery occlusion in rats.

BACKGROUND AND PURPOSE: In ischemic stroke, the ischemic crisis activates a cascade of events that are potentiated by reperfusion, eventually leading to cell death. The chief aim in this study was to investigate whether our new experimental model for stroke therapy, flushing the ischemic territory with saline before reperfusion, could minimize this damage by (1) reducing the inflammatory reaction and (2) improving regional microcirculation. METHODS: Stroke in Sprague-Dawley rats (n=39) was induced by a 2-hour middle cerebral artery occlusion with the use of a novel intraluminal hollow filament. Before 48-hour reperfusion, 20 of the ischemic rats received 7 mL isotonic saline at 23 degrees C or 37 degrees C infused into the ischemic area through the filament. Regional cerebral blood flow in cortex supplied by the right middle cerebral artery was measured by laser-Doppler flowmetry during ischemia and reperfusion. Leukocyte infiltration, microvascular plugging, and infarct volume were compared with the use of hematoxylin and eosin staining. Expression of intercellular adhesion molecule 1 (ICAM-1) was determined by immunocytochemistry. Neurological deficits were evaluated. RESULTS: After the prereperfusion infusion of saline, significantly (P<0.001) improved cerebral blood flow (105+/-12% of baseline) was obtained up to 48 hours after reperfusion, compared with 45+/-7% at 24 hours and 25+/-3% at 48 hours after reperfusion without local saline infusion. Significant (P<0.001) reductions in leukocyte infiltration (61%), vascular plugging (45%), infarct volume (approximately 65%), and neurological deficits were also produced. ICAM-1 expression in the infarct region was significantly (P<0.05) minimized by 37%. CONCLUSIONS: The reduced brain infarct and neurological deficits may be attributed to adequate reperfusion and ameliorated inflammation induced by local prereperfusion infusion.

Animals↗

PubMed2002

A model of global forebrain ischemia/reperfusion in the awake rat.

Anesthesia is an essential element during the induction of ischemia/reperfusion and cerebral blood flow (CBF) measurement in most animal models. Cerebral neuroprotection and intrinsic effects on CBF afforded by anesthetics are confounding variables in those models. A new model of global forebrain ischemia/reperfusion (GFIR) in awake rats is presented and characterized. Rats underwent permanent occlusion of the basilar, and the paired pterygopalatine, external carotid, and occipital arteries. Inflatable balloon occluders were inserted around both common carotids, the nine-vessel occlusion (9VO) preparation. A subgroup of 9VO rats underwent placement of a laser Doppler flowmetry (LDF) probe for measurement of cortical CBF. Twenty-four hours later, while awake, 9VO rats were subjected to 10 min of ischemia by occluding both common carotid arteries. Blood gases, glucose and hematocrit were analyzed before and during ischemia, and for up to 90 min during reperfusion. Behavioral observations and continuous LDF CBF and mean arterial blood pressure determinations during ischemia and reperfusion were made. Rats were rendered comatose and decerebrate rigidity was observed during 9VO. Following balloon deflation, rats immediately regained the righting reflex and achieved complete recovery in the next 24 h. Moderate hyperglycemia was observed at 5 min of ischemia and up to 90 min reperfusion in 9VO rats. LDF CBF decreased to 5% of baseline and remained unchanged during ischemia. The 9VO is a reproducible recovery model of GFIR. Behavioral and LDF CBF correlates are consistent and survival studies are feasible.

Anesthetics↗