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J Van Reempts

Publications and source records attributed to J Van Reempts.

At least 19 recordsLinked to original sources
PubMed2000

Validation of a closed head injury model for use in long-term studies.

To study pharmacotherapy of traumatic brain injury in rats, a modified closed head injury model was used that expresses clinically relevant features including intracranial hypertension and morphological alterations. Long-term survival under ethically acceptable conditions would greatly improve its clinical relevance. To ensure this goal with great reproducibility, the experimental protocol was adapted, in particular the impact-acceleration kinetics. Variations in impact-acceleration conditions were obtained by modifying the stiffness of the impact site and changing the height of a 400 g weight dropped from 51.5 to 31.5 cm (51.5/400; 31.5/400). Impact and acceleration were measured with a force sensor incorporated in a rigid dummy-rat and an accelerometer mounted on the platform onto which the animals are positioned. Significant correlation was shown between impact and acceleration. Accelerations obtained in rats were significantly lower than those in the dummy. Unlike the 51.5/400 group, in the 31.5/400 group no mortality or cranial fractures were observed. In both groups intracranial pressure rose to pathological values immediately after trauma and remained elevated longer than 24 h. Diffuse axonal injury developed in all groups and remained present for at least 7 days. By reducing the impact-acceleration conditions, post-traumatic complications were diminished, while the clinically important features were maintained.

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PubMed2000

Impaired autoregulation of cerebral blood flow in an experimental model of traumatic brain injury.

In order to study the pathophysiology and the intracranial hemodynamics of traumatic brain injury, we have developed a modified closed-head injury model of impact-acceleration that expresses several features of severe head injury in humans, including acute and long-lasting intracranial hypertension, diffuse axonal injury, neuronal necrosis, bleeding, and edema. In view of the clinical relevance of impaired autoregulation of cerebral blood flow after traumatic brain injury, and aiming at further characterization of the model, we investigated the autoregulation efficiency 24 h after experimental closed-head injury. Cortical blood flow was continuously monitored with a laser-Doppler flowmeter, and the mean arterial blood pressure was progressively decreased by controlled hemorrhage. Relative laser-Doppler flow was plotted against the corresponding mean arterial blood pressure, and a two-line segmented model was applied to determine the break point and slopes of the autoregulation curves. The slope of the curve at the right hand of the break point was significantly increased in the closed head injury group (0.751 +/- 0.966%/mm Hg versus -0.104 +/- 0.425%/mm Hg,p = 0.028). The break point tended towards higher values in the closed head injury group (62.2 +/- 20.8 mm Hg versus 46.9 +/- 12.7 mm Hg; mean +/- SD, p = 0.198). It is concluded that cerebral autoregulation in this modified closed head injury model is impaired 24 h after traumatic brain injury. This finding, in addition to other characteristic features of severe head injury established earlier in this model, significantly contributes to its clinical relevance.

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PubMed1998

Temporal changes in intracranial pressure in a modified experimental model of closed head injury.

OBJECT: The authors describe an experimental model of closed head injury in rodents that was modified from one developed by Marmarou and colleagues. This modification allows dual control of the dynamic process of impact compared with impulse loading that occurs at the moment of primary brain injury. The principal element in this weight-drop model is an adjustable table that supports the rat at the moment of impact from weights positioned at different heights (accelerations). The aim was to obtain reproducible pathological intracranial pressure (ICPs) while maximally reducing the incidence of mortality and skull fractures. METHODS: Intracranial pressure was investigated in different experimental settings, including two different rat strains and various impact-acceleration conditions and posttrauma survival times. Identical impact-acceleration injuries produced a considerably higher mortality rate in Wistar rats than in Sprague-Dawley rats (50% and 0%, respectively). Gradually increasing severity of impact-acceleration conditions resulted in findings of a significant correlation between the degree of traumatic challenge and increased ICP at 4 hours (p < 0.001, R2=0.73). When the impact-acceleration ratio was changed to result in a more severe head injury, the ICP at 4, 24, and 72 hours was significantly elevated in comparison with that seen in sham-injured rats (4 hours: 19.7+/-2.8 mm Hg, p=0.004; 24 hours: 21.8+/-1.1 mm Hg, p=0.002; 72 hours: 11.9+/-2.5 mm Hg, p=0.009). Comparison of the rise in ICP between moderate and severe impact-acceleration injury at 4 and 24 hours revealed a significantly higher value after severe injury (4 hours: p=0.008; 24 hours: p=0.004). Continuous recordings showed that ICP mounted very rapidly to peak values, which declined gradually toward a pathological level dependent on the severity of the primary insult. Histological examination after severe trauma revealed evidence of irreversible neuronal necrosis, diffuse axonal injury, petechial bleeding, glial swelling, and perivascular edema. CONCLUSIONS: This modified closed head injury model mimics several clinical features of traumatic injury and produces reliable, predictable, and reproducible ICP elevations with concomitant morphological alterations.

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PubMed1997

Altered Na(+)-channel function as an in vitro model of the ischemic penumbra: action of lubeluzole and other neuroprotective drugs.

Veratridine blocks Na(+)-channel inactivation and causes a persistant Na(+)-influx. Exposure of hippocampal slices to 10 microM veratridine led to a failure of synaptic transmission, repetitive spreading depression (SD)-like depolarizations of increasing duration, loss of Ca(+)-homeostasis, a large reduction of membrane potential, spongious edema and metabolic failure. Normalization of the amplitude of the negative DC shift evoked by high K+ ACSF 80 min after veratridine exposure was taken as the primary endpoint for neuroprotection. Compounds whose mechanisms of action includes Na(+)-channel modulation were neuroprotective (IC50-values in microM): tetrodotoxin 0.017, verapamil 1.18, riluzole 1.95, lamotrigine > or = 10, and diphenylhydantoin 16.1. Both NMDA (MK-801 and PH) and non-NMDA (NBQX) excitatory amino acid antagonists were inactive, as were NOS-synthesis inhibitor (nitro-L-arginine and L-NAME) Ca(2+)-channel blockers (cadmium, nimodipine) and a K(+)-channel blocker (TEA). Lubeluzole significantly delayed in time before the slices became epileptic, postponed the first SD-like depolarization, allowed the slices to better recover their membrane potential after a larger number of SD-like DC depolarizations, preserved Ca2+ and energy homeostasis, and prevented the neurotoxic effects of veratridine (IC50-value 0.54 microM). A concentration of lubeluzole, which was 40 x higher than its IC50-value for neuroprotection against veratridine, had no effect on repetitive Na(+)-dependent action potentials induced by depolarizing current in normal ACSF. The ability of lubeluzole to prevent the pathological consequences of excessive Na(+)-influx, without altering normal Na(+)- channel function may be of benefit in stroke.

Animals↗
PubMed1997

Intracranial pressure in a modified experimental model of closed head injury.

Intracranial pressure (ICP) was studied in a modified experimental model of closed head injury, in which the dynamic process of impact versus impulse loading was separately controlled. In this model, mortality of Wistar rats was considerably higher as compared to Sprague-Dawley rats subjected to similar traumatic conditions. Therefore Sprague-Dawley rats were used for all further experiments. Twenty-four rats, divided into 4 groups, underwent either sham or gradually increasing impact-acceleration trauma. Four hours after closed head injury, ICP measurements showed a significant correlation between the severity of the traumatic challenge and the resultant pressure rise (r2 = 0.731; p < 0.001). At the moment of impact there was a momentary blood pressure peak immediately followed by a transient period of hypotension. ICP measurements following directly to an impact-acceleration trauma, revealed an abrupt rise in ICP reaching pathological levels within 5 minutes. In conclusion, this modified model of closed head injury produces a predictable and reproducible pathologic ICP in Sprague-Dawley rats.

Animals↗
PubMed1997

Protection with lubeluzole against delayed ischemic brain damage in rats. A quantitative histopathologic study.

BACKGROUND AND PURPOSE: Cerebral ischemia may lead to glutamate-induced excitotoxic damage in vulnerable brain areas. Lubeluzole is not an N-methyl-D-aspartate antagonist but prevents postischemic increase in extracellular glutamate concentrations. The present study examined whether lubeluzole, administered after global incomplete ischemia in rats, is capable of preserving the structural integrity of CA1 hippocampus. METHODS: Ischemia was induced by bilateral carotid artery occlusion and severe hypotension for a duration of 9 minutes. Delayed neuronal cell death was histologically evaluated 7 days later. This was done by scoring acidophilic cell change and coagulative necrosis and by counting the number of surviving neurons in the CA1 subfield. Experiments were performed according to a paired design (13 animals per treatment group). RESULTS: Posttreatment with lubeluzole (0.31 mg/kg i.v. bolus at 5 minutes and 0.31 mg/kg i.v. infusion during 1 hour) resulted in significant neuroprotection. Whereas in the untreated rats there were 42 (median) viable neurons per millimeter CA1 layer in the left and 69 in the right hemisphere, in the drug-treated rats 99 viable neurons per millimeter were found in the left (P = .002) and 113 in the right hemisphere (P = .013). Histological scores, reflecting altered staining properties of the hippocampal cells, correlated strongly with the quantitative data, reflecting the structural integrity of CA1 pyramidal neurons. CONCLUSIONS: Lubeluzole, when administered after an ischemic insult in rats, protects vulnerable brain regions against delayed structural injury. The results support the potential clinical use of this new drug in stroke treatment.

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PubMed1996

In vivo noninvasive determination of abnormal water diffusion in the rat brain studied in an animal model for multiple sclerosis by diffusion-weighted NMR imaging.

In vivo NMR images of the rat brain were obtained using a NMR microscope (7 T) from SMIS (England). Four animals were imaged every 3-4 days during a pathological cycle (starting after induction and up to 37 days) of experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis. The EAE rats were weighted and clinically scored daily. We aimed at measuring the apparent diffusion coefficient (ADC) or the mean diffusivity (D) with a high accuracy, and within a reasonable experimental time frame, because of the clinical situation of the animals. Therefore, we fitted the ADC value from five diffusion-weighted images--with an experimental time of 17 min/image--and chose to apply diffusion-sensitizing gradients in a direction intersecting all fiber directions of the external capsule. With this, we also obtained high b-values. For the control rats, we obtained a statistical mean value of ADC = (388 +/- 16) 10(-12) m2/s for gray matter and a statistical mean value of (D) of (750 +/- 30) 10(-12) m2/s for white matter, measured in the external capsule. For the EAE rats, no alterations in ADC values of gray matter with increasing clinical scores were observed. Concerning white matter, as determined in the external capsule, there were no significant differences in (D) values between controls and EAE rats before clinical signs occurred. However, when clinical signs were observed, we could demonstrate a significant positive correlation between the clinical score and the (D) values in the external capsule. As the clinical signs became more severe, we measured a rise in water diffusion (increase in (D)) in the external capsule, which was accompanied by the occurrence of interstitial edema as revealed by a complementary histological study.

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PubMed1994

Histopathological characterization of photochemical damage in nervous tissue.

This paper discusses histological and ultrastructural changes produced by dye-sensitized photoreactions in the central and peripheral nervous system. Particular attention has been given to morphological outcome in experimental models which reproduce widespread clinical pathologies, e.g. stroke, spinal cord injury and peripheral neuropathy. Evaluation of structural alterations may not only help to characterize the evolution of these disease processes but also allow us to study possibilities of therapeutic intervention.

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PubMed1993

A new model of photochemically induced acute and reversible demyelination in the peripheral nervous system.

Acute photochemical demyelination accompanied by minor axonal degeneration was produced in rat sciatic nerve after topical application of the photosensitive dye Rose Bengal and focal illumination with cold light. Animals were sacrificed at different time periods after challenge and the exposed nerves prepared for light microscopic and ultrastructural evaluation. Important structural changes were already observed at 4-6 h. These included endoneurial swelling, diapedesis of neutrophils and monocytes, vacuolization and vesicularization of Schwann cell cytoplasm, lamellar separation of myelin sheaths, disintegration of axonal microtubules, and accumulation of vesicular material and mitochondria in the axoplasm. Disrupted myelin fragments were phagocytosed by macrophages which penetrated Schwann tubes at Day 3. Schwann cells proliferated and started to enwrap denuded segments of the axon. They were surrounded by redundant basal lamina, thrown into deep folds. Axons remained partly hypertrophic and contained many neurofilaments. A minority showed signs of degeneration. At Days 5-7 denudation was almost complete in the light-exposed nerve area but also in small distal nerve fascicles. After 1 month, axons in the illuminated area and distal to it were completely remyelinated although they had thinner sheaths. Exposure to increased light intensity resulted in deeper lesions and more extended anterograde damage, which also recovered within 1 month. All animals showed rapid functional deterioration which correlated with the severity and extent of structural damage. Recovery was slow and also depended on the degree of histologic damage. Neither control nerves nor sham-exposed nerves revealed signs of structural or functional changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Photochemically-induced cerebral infarction in the rat: comparison of NMR imaging and histologic changes.

The evolution of a photochemically induced cerebral thrombotic infarction was followed in rats during the first week after the insult by means of NMR imaging and histology. Heavily T2-weighted images provided an excellent lesion detection and a high specificity for the discrimination of different histological abnormalities. The T2-weighted images showed a brain lesion evolving during the first 24 h from a homogeneous hyperintense area, histologically corresponding to diffuse vasogenic and cytotoxic oedema with concomitant neuronal necrosis, to an iso-intense area with a hyperintense seam, which microscopically correlated with increased vascular permeability at the periphery of the lesion. The hyperintense seam was observed up to day 7, but at that time coincided with gliomesodermal repair reaction which could be verified histochemically and ultrastructurally. It may be concluded that NMR-micro-imaging at a moderately high field, enables early detection and adequate follow-up of small cerebral infarctions in rats.

Animals↗
PubMed1993

Learning performance at different time periods after hypoxia in infant rats.

Infant rats were exposed to hypoxia. At different time periods after the hypoxic aggression the animals were subjected to a one-way active avoidance task consisting of 3 daily training sessions. Learning performance of hypoxic rats, expressed as the number of avoidances per 10 trials, was significantly decreased in all the sessions at posthypoxic day 35 (P < 0.001). The rate to which learning behaviour was affected by hypoxia was comparable among all 3 sessions in both groups. Histological evaluation of hippocampus and cortex at day 7 and day 35 after hypoxic exposure, did not reveal detectable structural changes. It can be concluded from this study that hypoxia, induced in 21 day old rats leads to learning performance deficits in the adult animal.

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PubMed1992

Synaptic plasticity in rat hippocampus associated with learning.

Rats subjected to a one-way active avoidance task consisting of 3 daily training sessions, showed obvious shape changes in dendritic spines of the hippocampal supragranular molecular layer. Performance, expressed as the number of avoidances per 10 trials, significantly improved in the second and third session (P < 0.001). In trained animals, at the end of the third session, the amount of perforated concave synapses significantly increased as compared to untrained controls (P < 0.05). When compared with a group of sham-shocked rats, the increase was less pronounced. The length of the postsynaptic density in both, perforated and non-perforated synapses, significantly increased in comparison with untrained control and sham-shocked animals (perforated: P < 0.005; non-perforated: P < 0.05). The results are indicative for the existence of synaptic remodeling and turnover in rats subjected to one-way active avoidance training.

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PubMed1992

Neocortical localization of tactile/proprioceptive limb placing reactions in the rat.

The present study was aimed at delineating the neocortical substrate of tactile/proprioceptive limb placing reactions in rats by means of behavioral tests that excluded the participation of facial stimuli in limb function. Using a photochemical technique, we made unilateral focal lesions in the frontal and parietal neocortex. Fore- and/or hindlimb placing deficits resulted from damage to a fronto-parietal region lying between the medial agranular cortex and the primary somatosensory (whisker barrel field) cortex. When the antero-posterior coordinate was varied from 4 mm anterior to 1 mm posterior to bregma, tactile/proprioceptive forelimb dysfunction was more pronounced after damage to the parietal forelimb area, but lesions confined to the frontal lateral agranular cortex also yielded clear-cut forelimb placing deficits. Damage to either area alone allowed for partial recovery of forelimb function. However, following combined, total destruction of both frontal and parietal forelimb areas, forelimb deficits did not recover. This resembled the irreversible hindlimb deficits after near-total destruction of the parietal hindlimb area. Damage to the medial agranular cortex left limb placing intact. Likewise, for as long as the medial edge of lesions to the whisker barrel field did not come closer than 3 mm to the midline, thus remaining outside the parietal hindlimb area, limb placing remained normal. This sharp medial and lateral delineation of the cortical substrate subserving tactile/proprioceptive limb placing coincides with the borders of a thick, dense subfield of large pyramidal neurons in the deeper parts of layer V. Limb placing remained intact when medial agranular cortex lesions damaged only 30% of that subfield, whereas 70% destruction of that layer following more laterally placed lesions in the parietal hindlimb area produced irreversible hindlimb dysfunction. The severity of hindlimb placing deficits was related to the amount of incursion by whisker barrel field lesions into the subfield of deep layer V large pyramidal neurons. Finally, very large lesions of the occipital cortex did not affect tactile/proprioceptive limb placing. We discuss the neocortical areal and laminar specificity of tactile/proprioceptive limb function in the context of recent neuroanatomical and electrophysiological findings, and their relevance to normal cortical function, recovery from neocortical stroke (including diaschisis), and age-related cortical dysfunction.

Animals↗
PubMed1992

Microwave-enhanced silver staining of degenerating neuronal processes.

A simple and rapid method for light and electron microscopic visualization of degenerating neuronal processes and axon terminals is described. Hundred-micrometer vibratome sections of perfusion-fixed rat brain were incubated briefly in a 5% silver nitrate solution in a conventional microwave oven. After a rinse in 1% acetic acid, the sections were silver enhanced. Differentiation and counterstaining was done respectively in ethanol 100% and cresyl violet. In the light microscope, degenerating neuronal processes appeared as black dots against a clear background. Areas of calcification were also positively stained. The presence of silver deposits in degenerating presynaptic terminals and dendrites was confirmed ultrastructurally.

Animals↗
PubMed1992

The course of vasospasm following subarachnoid haemorrhage in rats. A vertebrobasilar angiographic study.

The course of vasospasm following subarachnoid haemorrhage in rats was studied using vertebrobasilar angiography. Wistar and Sprague Dawley rats were compared with respect to vasospastic response after bleeding. A more pronounced vasospasm was found in Sprague Dawley rats. In order to avoid a possible toxic effect on the contrast medium, only one angiogram per animal was initially performed. However, a comparison with the results obtained in a separate series of non-challenged animals demonstrated a difficulty due to high variability in basilar artery size in the latter group. Therefore, vasospasm can be more readily shown if multiple angiograms are used in the same animal so that the vasospasm can be expressed as a percentage of the initial diameter of the basilar artery. It was found that multiple angiograms are well tolerated when non-ionic contrast media are used.

Animals↗
PubMed1992

Haemodynamic, intracranial pressure and electrocardiographic changes following subarachnoid haemorrhage in rats.

Experimental induction of subarachnoid haemorrhage in rats resulted in acute haemodynamic changes. Heart rate decreased concomitantly with a rise in arterial blood pressure. Intracranial pressure increased and consequently cerebral perfusion pressure dropped. These changes as well as the observed electrocardiographic (ECG) changes were comparable to those reported in patients. Apart from blood also saline, when introduced into the cisterna magna, was able to elicit such abnormalities. The haemodynamic and electrocardiographic changes, which result from subarachnoid haemorrhage, may even become aggravated, when repetitive injections of blood or saline are given into the cisterna magna and when cerebral angiography is performed prior to induction of the subarachnoid haemorrhage. Chronic intracranial pressure monitoring during the 48 hours following subarachnoid haemorrhage revealed no significant rise in pressure. A thorough control of the experimental conditions is thus of utmost importance in order to give a valid interpretation of the observed anomalies.

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