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T Fortin

Publications and source records attributed to T Fortin.

28 records · Page 2Linked to original sources
PubMed1992

Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats.

Young and aged rats were subjected to cerebrovascular insufficiency (CVI) for 3 and 9 weeks. At the end of each time period, local cerebral blood flow (lCBF), spatial memory function, 31P- and 1H-NMR spectroscopy and imaging of the brains were evaluated in vivo. Morphometric counts of CA1 hippocampal neuron damage and staining for glial fibrillary acidic protein (GFAP) were done post-mortem. Results show that after 3 weeks of CVI, cortical and hippocampal lCBF was significantly reduced in young and aged animals respectively. In addition, young and aged rats at 3 weeks following CVI showed spatial memory deficits in the Morris water maze and elevation of 31P-phosphomonoester as measured by non-invasive NMR spectroscopy. At the same time period, in vivo 1H-microimaging (MRI) of brains showed areas of high signal intensity (suggesting local edema) localized asymmetrically to the right hippocampal region in young and aged CVI rats. Morphometry of the hippocampal CA1 sector at post-mortem confirmed the in vivo MRI changes and demonstrated that a significant percentage of the CA1 pyramidal cells were damaged after CVI. Nine weeks after CVI, hippocampal CBF reductions, spatial memory impairment, spectroscopic-microimaging changes and CA1 sector cell damage continued to be observed in the aged animals but were resolved in the young rat brains. In addition, GFAP immunoreaction progressively increased in the hippocampus of aged rats subjected to CVI for 9 weeks. It is concluded that cognitive, metabolic and morphologic damage was significantly more severe and longer lasting in aged than young rat brain after chronic CVI. The deficits observed in this rat model appear to mimic the early pathology reported in Alzheimer's disease and suggest that the present model could provide fundamental clues relative to the etiology and possible management of this dementia.

Aging↗
PubMed1992

The no-reflow phenomenon is a post-mortem artifact.

Post-ischemic reperfusion impairment, ("no-reflow phenomenon"), was studied in rats subjected to 8-30 minutes of global brain ischemia. During ischemia, rapid and complete loss of cerebral blood flow, EEG and 31P-high energy phosphates (ATP/PCr) was observed. Brain intravascular perfusion defects were examined by injecting carbon black intravenously in a group of rats with stable cardiopulmonary function and in another group subjected to rapid thoracotomy and intraarterial infusion of the carbon marker. Results indicate that global brain ischemic or non-ischemic control rats given intraarterial carbon black after thoracotomy had varying degrees of vessel filling defects in brain resulting in "pale tissue areas" suggestive of impaired perfusion (no-reflow). All rats given carbon black intravenously whether global brain ischemic or not, showed normal cerebrovascular filling of the carbon black and absence of "pale tissue areas". In addition, post-ischemic cerebral reperfusion following 8-30 minutes global brain ischemia can reverse neuroelectric, energy metabolite and cerebral blood flow loss in rats whose cardiopulmonary function is not compromised. These findings indicate that the "no-reflow phenomenon" is an agonal or post-mortem artifact observed in the presence of cardiopulmonary failure.

Adenosine Triphosphate↗
PubMed1991

Return of ATP/PCr and EEG after 75 min of global brain ischemia.

Acute, progressive global brain ischemia was induced in awake or anesthetized rats for 5-75 min. Ischemia was achieved with a subclavian-carotid artery occlusion technique (SCOT). After thoracotomy, both subclavian arteries (proximal to their vertebral branches) were tied-off and carotid artery catheter-snares installed. Results show progressive morphological, physiological and neurochemical damage when CBF was reduced from preischemic levels of 115 ml to 0 blood flow. 31P magnetic resonance spectroscopy of high energy phosphate metabolites in vivo showed loss of PCr and beta-ATP signals after 6 min brain ischemia. Energy metabolite levels, EEG and CBF normalized within hours after reperfusion. Degree of neuropathologic damage to hippocampal region appeared linearly related to the ischemic duration of ischemia. Thus, acute global brain ischemia resulted in loss of high energy phosphate metabolites, EEG and neuronal integrity in the hippocampal subfields. Reperfusion following short (5 min) or long (75 min) periods of global brain ischemia induced return of 31P-spectra, EEG and CBF to normal but was unable to reverse all of the neuronal damage at the end of the 72-h observation period.

Adenosine Triphosphate↗
PubMed1991

Partial or global rat brain ischemia: the SCOT model.

A model for inducing partial (PBI) or global brain ischemia (GBI) in awake or anesthetized rats was obtained by ligating one subclavian and both carotid arteries (for PBI) or both subclavian-carotid arteries (for GBI). Rats were intubated and ventilated mechanically then subjected to a midline ventral incision from larynx to xiphoid process. The thorax was entered to expose the aortic arch and either one or both subclavians were ligated to eliminate each vertebral artery supply to brain. After chest closure the common carotid arteries were exposed and immediately ligated or else catheter snares were installed to induce ischemia at a later date. PBI was induced in 3 groups of rats for 7, 30 and 60 days while GBI was given for 5, 10, 30 and 75 minutes in 4 other groups. EEG became flat within 15 seconds after GBI and cortical cerebral blood flow (CBF) was reduced to "zero." EEG was unaffected after PBI but cortical CBF was reduced from a mean 118 ml/100 g tissue/min to 77 ml after 7 days. Morphological damage of CA1 hippocampal neurons after GBI or PBI was found reproducible and time dependent on ischemic duration. Acute cell damage rose from 5-95% in CA1 as GBI duration increased from 5-75 minutes. Similarly, chronic cell damage of CA1 increased as ischemic duration continued from 7-60 days in rats subjected to PBI. The advantages of the present model provide the option of inducing partial or global brain ischemia and of introducing postischemic reperfusion in awake or anesthetized preparations without the use of drugs, blood pressure manipulation or direct contact with brain tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Associated norepinephrine loss following calcium-induced spinal paralysis.

A 10% calcium chloride solution or normal physiological saline was instilled onto the intact dorsal surface of the spinal cord via a specially constructed catheter-canopy system fixed above the T9 level in conscious rats. Within 5 min after calcium instillation rats developed flaccid paralysis of the lower limbs with sensory loss. Sensory loss was accompanied by abnormal or negative evoked potentials. Rats instilled with physiological or 10% sodium chloride remained normal. Rats were sacrificed at 1, 16 and 48 h post-calcium exposure and following full functional recovery from paralysis. Spinal cords were removed for histologic and high-performance liquid chromatography (HPLC) analysis. Histologic examination for catecholamines using SPG histofluorescence showed loss of catecholamine-containing varicosities in gray matter below calcium exposure which returned to normal levels upon sensorimotor recovery of hindlimbs about 14 days pce. Light microscopic examination of vascular permeability and general morphology of cord tissue axons and neurons remained normal in calcium and saline instilled rats. HPLC analysis of spinal cord below calcium exposure, also showed norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol (MHPG) tissue level reductions which returned to normal upon sensorimotor recovery of paralysis about 2 weeks later. No significant changes were noted in dopamine or serotonin levels in any group. Our findings suggest an impairment of ascending and descending tract transmitter transport, specifically reflected in the noradrenergic bulbospinal pathway. The results implicate a neurofilament-microtubule disassembly in axonal cytoskeleton triggered by the sudden calcium influx.

Animals↗
PubMed1988

Laser or razor? A novel experimental peripheral nerve repair technique.

An operative repair technique for crushed sciatic nerve in the rat was used to examine whether removal of the damaged tissue could be better achieved with a low wattage CO2 laser or a blade. This approach was compared to results in rats undergoing conventional end-to-end nerve anastomosis using a microsurgical approach. Crushed sciatic nerves were exposed bilaterally 24 hours after injury and treated as follows. A longitudinally split polyethylene catheter was placed under the nerve, which was fixed to the catheter with 9-0 stitches placed away from lesion area; the nerve was bathed in ice-cold polyvinyl alcohol/chlorpromazine (PVA/CPZ) solution. After the nerve was crushed, the lesioned tissue was removed using laser pulses or a thin blade. A collagen matrix was used to fill the gap, and the preparation was covered and allowed to recover for 6 weeks. End-to-end anastomosis was done following same parameters, but with omission of the nerve catheter, PVA/CPZ solution, and collagen matrix; these nerves were reunited using epineurial stitches. High performance liquid chromotography (HPLC) analysis of each group showed that the laser approach reduced the levels of norepinephrine distal to the lesion, least, suggesting better regeneration of proximal axonal growth. Morphological and neuroelectric findings, although suggestive, showed no significant differences between laser and blade repair, a finding that reinforces the idea that such endpoints are not as sensitive as chemical assays of tissue transmitter levels such as HPLC. Laser or blade repair using nerve-catheter fixation and collagen bridge matrix was superior to end-to-end nerve anastomosis when morphological, neuroelectric, and HPLC values were compared in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Cleavage of amyloid precursor protein elicited by chronic cerebral hypoperfusion.

In the present study, we sought to determine whether low-grade, chronic vascular insufficiency induced in a rodent model of chronic cerebrohypoperfusion is sufficient, in and of itself, to trigger cleavage of the amyloid precursor protein (APP) into beta A-sized fragments. We report that chronic two vessel occlusion (2VO) results in progressive accumulation of beta A peptides detected by Western analysis in aged rats correlating with a shift in the immunohistochemical localization of APP from neurons to extracellular deposits in brain parenchyma. These data indicate that the 2VO paradigm reproduces features of beta A biogenesis characteristic of sporadic Alzheimer's disease.

Amino Acid Sequence↗
PubMedDate not supplied

Pinealectomy: behavioral and neuropathological consequences in a chronic cerebral hypoperfusion model.

This experiment determined if pinealectomy (PX) affects the consequences of chronic, moderate brain ischemia. Rats were pinealectomized at 25 days of age and trained at 9 months on a tactile radial maze. They then underwent permanent occlusion of the common carotid arteries (2VO) or sham surgery, followed by maze retraining and then neurohistological assessment at 16 months. Combined PX + 2VO rats committed more working memory errors on the maze. 2VO itself caused a 10% reduction in hippocampal CA1 pyramidal cell number. PX alone caused a 21% reduction. Combined PX and 2VO caused the greatest reduction (32%) of CA1 cells. Similar results were seen for CA4. PX also increased glial fibrillary acidic protein immunoreactivity in both CA1 and CA4. Thus PX not only augmented the consequences of chronic brain ischemia but notably, PX itself caused hippocampal damage. These effects seemed not to result from the small cortical lesion caused by the PX procedure. The results are consistent with the hypothesis that endogenous melatonin is a neuroprotectant in the aging brain.

Animals↗
PubMedDate not supplied

Perinatal manganese exposure: behavioral, neurochemical, and histopathological effects in the rat.

Manganese chloride (Mn) was dissolved in the drinking water (0, 2, or 10 mg/ml) of dams and their litters from conception until postnatal day (PND) 30. Parturition was uneventful in the Mn-exposed rats and no physical abnormalities were observed. The rats exposed to 10 mg/ml Mn showed a 2.5-fold increase in cortical Mn levels. Their weight gain was attenuated from PND 9-24 and they were hyperactive at PND 17. Neither the 2 nor the 10 mg/ml Mn-exposed groups differed from the controls on the elevated plus apparatus or on the Morris water maze and the radial arm maze. Brain monoamine levels and choline acetyltransferase activity were affected. Tyrosine hydroxylase immunohistochemistry showed that dopamine cells of the substantia nigra were intact. Glial fibrillary acidic protein immunoreactivity was not increased in cortex, caudate, and hippocampus. However, both the low- and high-dose Mn-exposed groups showing thinning of the cerebral cortex. This could have resulted from perinatal malnutrition or from a direct effect of Mn on cortical development.

Analysis of Variance↗