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J Towfighi

Publications and source records attributed to J Towfighi.

At least 37 records · Page 2Linked to original sources
PubMed1995

Temporal evolution of neuropathologic changes in an immature rat model of cerebral hypoxia: a light microscopic study.

The sequential evolution of neuropathologic changes was studied in an immature model of cerebral hypoxia-ischemia. According, 7-day postnatal rats were subjected to unilateral common carotid artery ligation combined with 2 h of hypoxia (breathing in 8% oxygen) and their brains were examined by light microscopy at recovery intervals ranging from 0 to 3 weeks. Immediately following hypoxia, a large area with a pale staining border was noted occupying most of the cerebral hemisphere ipsilateral (IL) to the occluded common carotid artery; in approximately half of the brains the dorsomedial cortex of the contralateral (CL) hemisphere was also involved. Most neurons in the pale area had nuclei containing a coarse granular condensation of chromatin. Within a few hours, the majority of neurons in the IL hemisphere had developed pyknotic nuclei and clear or eosinophilic perikarya. After 24 h these changes had evolved in the majority of brains into coagulation necrosis (infarction) in the IL hemisphere and foci of selective neuronal necrosis in the CL cortex. Within a few days infarcts became partially cavitated, and by 3 weeks a smooth-walled cystic infarct had developed. Activated microglia/macrophages and reactive astrocytes were first seen at 4 and 24 h, respectively. No parenchymal neutrophilic infiltrate was seen at any time point.

Animals↗
PubMed1995

Effect of hypoxia/ischemia on bicuculline-induced seizures in immature rats: behavioral and electrocortical phenomena.

The relation between hypoxia/ischemia and subsequent alterations in seizure susceptibility in developing brain remains unclear. We assessed the behavioral and electrocorticographic (ECoG) effects of hypoxic/ischemic brain damage on bicuculline (BIC)-induced seizures in 7-day postnatal rats, and determined maturational changes in seizure susceptibility, behavior and ECoG activity. Rat pups were subjected to unilateral common carotid artery ligation, followed by exposure to 8% O2 at 37 degrees C for 2 h, an insult that produces brain damage in the cerebral hemisphere ipsilateral to carotid artery occlusion. The experimental group consisted of rat pups previously subjected to hypoxia/ischemia; control littermates received neither arterial ligation nor systemic hypoxia. Experimental animals received 4, 5, or 6 mg/kg BIC subcutaneously (s.c.) at 2 and 24 h, and at 3, 7, and 21 days of recovery from hypoxia/ischemia. Two animals at each interval of recovery, 1 each from the experimental and control groups, were used for ECoG monitoring. After BIC injection, animal behavior was observed for 2 h. Behaviors and seizures were classified in five categories based on severity, duration, and character: 1, mild irritability; 2, few clonic seizures and agitation; 3, few tonic-clonic seizures with swimming movements; 4, frequent tonic-clonic seizures with apneic episodes; 5, continuous tonic-clonic seizures and death. Rat pups previously subjected to hypoxia/ischemia had lesser seizure susceptibility than controls at 2-h recovery (p < 0.05) and greater susceptibility than controls at 24 h (p < 0.05). Tonic seizures were prominent at 2 and 24 h in both the experimental and control groups, whereas lesion-sided circling was prominent only in the hypoxic/ischemic rat pups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effect of status epilepticus on hypoxic-ischemic brain damage in the immature rat.

Seven-day postnatal rats were subjected to unilateral common carotid artery ligation, 3 h after which they were subjected to hypoxia with 8% oxygen at 37 degrees C for 2 h. Thereafter, they received multiple s.c. injection(s) of bicuculline (6 mg/kg) adequate to produce behaviorally apparent seizures lasting greater than 1 h (status epilepticus). Repeated episodes of status epilepticus at 2, 6, and 12 h of recovery from hypoxia-ischemia (HI) produced a mortality rate of 53%. Among the survivors, there was no statistically significant difference in the extent of brain damage between convulsing and non-convulsing HI controls, analyzed at 30 d of age. Histopathologic examination for acute lesions also indicated no difference in the severity of brain damage between dead and surviving rat pups subjected to status epilepticus, indicating that mortality was not related to the severity of prior HI brain damage. Those immature rats that died during status epilepticus exhibited lower blood glucose concentrations (1.75 +/- 0.35 mmol/L) compared with surviving, convulsing animals (4.25 +/- 0.51 mmol/L; p = 0.016). Glucose supplementation (0.1 mL of 50% glucose) early during status epilepticus improved survival and significantly prolonged seizure activity (90 +/- 14 min) compared with non-glucose treated, convulsing littermates (47 +/- 10 min; p = 0.02). Glucose supplementation did not increase the extent of brain damage despite improved survival and increased duration of seizure activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Laminin beta 2 chain and adhalin deficiency in the skeletal muscle of Walker-Warburg syndrome (cerebro-ocular dysplasia-muscular dystrophy).

Muscular dystrophy may be caused by disturbances in a number of muscle proteins that appear to be part of a chain of interacting molecules that includes cytoskeletal, cell membrane, and basement membrane components. We found that the skeletal muscle cells in two cases of Walker-Warburg syndrome were severely deficient in the laminin beta 2 chain and in adhalin. The findings indicate that these two proteins are key molecules in the interactive protein complex conferring muscle stability and cell survival.

Abnormalities, Multiple↗
PubMed1995

MR of giant arachnoid granulation, a normal variant presenting as a mass within the dural venous sinus.

We report three cases of masses within the cerebral dural venous sinuses shown with either MR or angiography. The dural venous sinuses of 10 patients without known venous disease were examined at autopsy. In two patients, three giant arachnoid granulations were identified. On the basis of the literature and our limited autopsy series, we suggest that these lesions identified at imaging are giant arachnoid granulations, normal variants of no known clinical significance.

Adult↗
PubMed1995

Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: an experimental study in the immature rat.

BACKGROUND AND OBJECTIVE: Clinical investigations suggest that premature infants who require mechanical ventilation from respiratory distress syndrome are at increased risk for periventricular leukomalacia if hypocapnia occurs during respiratory management. The question remains as to the contribution of hypocapnia to hypoxic-ischemic brain damage and whether or not hypercapnia is neuroprotective. METHODS: Seven-day postnatal rats underwent unilateral common carotid artery ligation followed thereafter by exposure to systemic hypoxia with 8% oxygen (O2) combined with either 0, 3, 6, or 9% carbon dioxide (CO2) for 2.5 hours at 37 degrees C. Survivors underwent neuropathologic examination at 30 days of postnatal age, and their brains were categorized as follows: 0 = normal; 1 = mild atrophy; 2 = moderate atrophy; 3 = atrophy with cystic cavitation < 3 mm; 4 = cystic cavitation > 3 mm of the cerebral hemisphere ipsilateral to the carotid artery ligation. The width of the ipsilateral hemisphere also was determined on a posterior coronal section and compared with that of the contralateral hemisphere to ascertain the severity of cerebral atrophy/cavitation. Data were analyzed by linear models. RESULTS: CO2 tensions averaged 26, 42, 54, and 71 mm Hg in the 0, 3, 6, and 9% CO2 exposed animals, respectively, during systemic hypoxia. Blood O2 tensions during hypoxia were not different among the four groups and averaged 34.7 mm Hg. Neuropathologic results showed that 30/38 (79%) rats exposed to 3% CO2 showed either no or mild brain damage compared with 13/33 (39%) controls (0% CO2). Cystic cavitation occurred in only four CO2 exposed rat pups compared with 14 controls (P = .001). At 6% CO2 exposure, all of 20 rat pups showed either no damage or mild atrophy compared with controls (P < .001); and at 9% CO2 exposure, 19/23 (83%) rat pups showed no or mild damage compared with controls (P < .001). The data also showed that the greatest reduction in brain damage occurred in immature rats exposed to 6% CO2 with slightly less protection at 9% CO2 (P = .012), the latter comparable with the severity of brain damage sustained by animals inhaling 3% CO2. Analyses of coronal width ratios at each CO2 exposure provided results comparable with those of the gross neuropathology scores. CONCLUSIONS: The results indicate that in an immature rat model normocapnic cerebral hypoxia-ischemia is associated with less severe brain damage than in hypocapnic hypoxia-ischemia and that mild hypercapnia is more protective than normocapnia. The findings in an experimental model merit further animal investigations as well as a clinical reappraisal of the ventilatory management of sick newborn human infants.

Administration, Inhalation↗
PubMed1995

The asymmetric mamillary body: association with medial temporal lobe disease demonstrated with MR.

PURPOSE: To determine whether mamillary body atrophy is caused by deafferentation of the mamillary body in patients with mesial temporal sclerosis. METHODS: We studied 36 patients with thin-section MR to assess mamillary body symmetry. These patients included 10 control subjects without seizures and 26 patients with a history of seizures. Thin-section T1 scans were available for all cases. The patients with epilepsy underwent axial and coronal T2 scans as well. RESULTS: In five of eight cases with prior medial temporal lobe resection for intractable epilepsy, there was evidence of unilateral mamillary body atrophy ipsilateral to the resection. Similar findings were evident in three of six patients with MR findings of mesial temporal sclerosis without surgery. Two patients with medial temporal stroke or tumor also had ipsilateral mamillary body atrophy. CONCLUSION: These findings provide support for the proposed mechanism of mamillary body atrophy caused by prior medial temporal lobe injury.

Adult↗
PubMed1994

Cerebral energy metabolism during hypoxia-ischemia correlates with brain damage: a 31P NMR study in unanesthetized immature rats.

The association between the ultimate brain damage resulting from unilateral hypoxic-ischemic insult (HI) and the changes in high-energy metabolites, measured by noninvasive phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy during the insult, was evaluated in 7-day postnatal rats. When the NMR metabolite levels were integrated over the last 1.5 h out of 2.5 h of HI, there was a significant correlation of both the estimator of phosphorylation potential (P < 0.001) and ATP levels (P < 0.01) with histologic score of damage and area morphometry. In particular, the development of cerebral infarction could be predicted from the NMR evaluation (P < 0.005). These findings suggest that a large disturbance in cellular energy metabolism is a prerequisite for the subsequent neuropathological alterations in this model.

Adenosine Triphosphate↗
PubMed1994

The effect of focal cerebral cooling on perinatal hypoxic-ischemic brain damage.

We describe a method of focal cooling of the head and its effects on hypoxic-ischemic cerebral damage in neonatal rat. Focal cooling of the head was obtained by positioning a catheter under the scalp ipsilateral to the ligated common carotid artery and by running cold water through the catheter during 2 h of systemic hypoxia. Hypoxia was produced in neonatal rats by breathing 8% oxygen for 2 h in a 37 degrees C chamber. Animals underwent focal cooling with ipsilateral scalp temperatures ranging from 22 degrees C to 35 degrees C. Temperature recordings from the ipsilateral scalp, cerebral hemisphere (dorsal hippocampus) and core (rectal) were obtained. The results suggest that the method is effective in cooling of brain and also to a lesser extent in lowering of the core temperature. At a mean scalp temperature of 28 degrees C, mean hippocampal temperature in hypoxic rat was 29.5 degrees C and mean core temperature in hypoxic rat was 32.8 degrees C. At a lower scalp temperature of 22 degrees C, mean hippocampal temperature in hypoxic rat was 24.7 degrees C and mean core temperature was 31.3 degrees C. Neuropathologic examination 3-4 days following hypoxia-ischemia showed that focal cooling with a scalp temperature of lower than 28 degrees C completely protected from brain damage, and that there was a trend towards greater damage with higher scalp temperatures.

Animals↗
PubMed1994

Adipose tissue and smooth muscle in a primitive neuroectodermal tumor of cerebrum.

We describe a case of an occipital lobe primitive neuroectodermal tumor (PNET) in a 60-year-old man with immunocytochemical evidence of neuronal, glial, smooth muscle and adipose tissue differentiation in the primary tumor and its metastases. This is the first case of PNET of cerebrum in which adipose tissue and smooth muscle has been demonstrated. The possible cells of origin for these mesenchymal elements is discussed.

Adipose Tissue↗
PubMed1994

Effect of unilateral perinatal hypoxic-ischemic brain damage on the gross development of opposite cerebral hemisphere.

The effect of unilateral perinatal cerebral hypoxic-ischemic damage on the gross development of the opposite hemisphere was investigated in immature rats. Eight-day-old rats underwent unilateral common carotid artery ligation followed by exposure to hypoxia (8% oxygen) ranging from 1 to 2 h at 37 degrees C. The animals were sacrificed 3 weeks later, and brain damage was assessed histologically, by weighing the cerebral hemispheres, and by measuring hemispheric cross-sectional area and diameter as well as the thickness of neocortex. There were no significant differences in either the size or cortical thickness of the cerebral hemisphere contralateral to the damaged hemisphere compared to those of controls. The results are comparable to the effect of unilateral perinatal hemispheric decortication and hemispherectomy on the growth of the contralateral hemisphere and suggest that: (1) perinatal damage to one cerebral hemisphere does not significantly alter the size of the other hemisphere, and (2) the contralateral hemisphere may be used as a 'normal' reference in evaluating the extent of atrophy or infarction of a cerebral hemisphere damaged earlier by perinatal hypoxia-ischemia.

Animals↗
PubMed1994

Differences in intraischemic temperature influence neurological outcome after deep hypothermic circulatory arrest in newborn dogs.

BACKGROUND AND PURPOSE: Hypothermia to core temperatures ranging from 16 degrees C to 24 degrees C has become an established procedure to extend the "safe" interval of cardiac arrest during open heart surgery in human infants. The present experiment was designed to ascertain whether differences in core (rectal) temperature during hypothermic circulatory arrest influence the presence and extent of ischemic brain damage in newborn dogs. METHODS: Newborn dogs (postnatal age, 3 to 5 days) were anesthetized with halothane (4% induction; 0.5% maintenance), intubated, paralyzed, and artificially ventilated with 70% nitrous oxide/30% oxygen. Thereafter, the dogs were surface cooled with ice packs to either 16 degrees C (n = 6), 20 degrees C (n = 8), or 24 degrees C (n = 6). The dogs then were subjected to circulatory arrest for 1.75 hours by the intravenous injection of KCl, following which they were resuscitated with intravenous NaHCO3 and epinephrine, artificial ventilation, and closed chest cardiac massage. Those dogs that survived for 8 hours of recovery (n = 16) underwent neurobehavioral examination followed by perfusion-fixation of their brains for pathological analysis. RESULTS: All newborn dogs were successfully resuscitated after 1.75 hours of cardiac arrest, rewarmed to 37 degrees C, and ultimately weaned from anesthesia and ventilatory support. Four dogs sustained secondary systemic complications with death at 4 to 7 hours. All surviving dogs remained stable, with systemic blood pressure, heart rate, arterial oxygen, and acid-base balance within the normal, normothermic range. Of the 16 surviving dogs, all except 1 showed histological evidence of brain damage at 8 hours of recovery. Morphometric analysis of the number of necrotic neurons in the vulnerable gray matter structures showed the greatest damage to cerebral cortex at 24 degrees C and the least damage to this structure at 16 degrees C by either regression analysis (r = .62; P = .01) or a repeated-measures model (P = .008). The extent of damage to the caudate nucleus was similar in the three temperature groups, while damage to the amygdaloid nucleus was greater at 24 degrees C compared with 20 degrees C but with no difference in the severity of damage between 20 degrees C and 16 degrees C. A close correlation existed between neurobehavioral deficits in the surviving dogs and the severity of damage to the cerebral cortex (r = .72; P = .001). CONCLUSIONS: The findings indicate that differences in intraischemic core temperature during deep hypothermic circulatory arrest influence the severity of damage to the cerebral cortex of newborn dogs. Specifically, the lower the temperature below 24 degrees C, the more protected the structure from ischemic injury. Furthermore, the greater the cortical damage, the more severe the neurobehavioral deficits. Such was not the case for the amygdaloid nucleus and especially for the caudate nucleus. Accordingly, differences in core temperature, even at very low levels, appear critical for optimal protection of the newborn brain during hypothermic circulatory arrest.

Animals↗
PubMed1993

Low diagnostic yield of sural nerve biopsy in patients with peripheral neuropathy and primary amyloidosis.

Patients with primary amyloidosis may develop peripheral neuropathy as an early feature. Sural nerve biopsy is reported to be a sensitive method for diagnosing amyloidosis in such patients. We identified nine patients, ultimately diagnosed as having amyloidosis, who were referred for peripheral neuropathy of undetermined etiology. In six, a sural nerve biopsy demonstrated no amyloid. Subsequent examination of other tissue or of the contralateral sural nerve eventually resulted in the correct diagnosis. We conclude that sural nerve biopsy may be less sensitive than previously believed for the diagnosis of amyloidosis in patients with peripheral neuropathy secondary to amyloid. When the clinical suspicion of amyloidosis is high, a nondiagnostic sural nerve biopsy should not discourage the performance of further investigative studies.

Aged↗
PubMed1993

Neuropathologic aspects of hypothermic circulatory arrest in newborn dogs.

A model of hypothermic circulatory arrest with recovery has been developed in the newborn dog. Eleven puppies were anesthetized with halothane, paralyzed and artificially ventilated with 70% nitrous oxide -30% oxygen to paO2 > 60 mm Hg, paCO2 = 33-42 mm Hg and pHa = 7.35-7.42. Animals were surface cooled to 20 degrees C, following which cardiac arrest was effected with i.v. KCl. Dogs remained asystolic without ventilation for 1.0, 1.5 or 1.75. Resuscitation was accomplished with closed-chest compression, mechanical ventilation, i.v. epinephrine and NaHCO3, and rewarming to 37 degrees C. Thereafter, the puppies were allowed to recover from anesthesia and maintained for either 18-22 h (n = 9) or 72 h (n = 2), at which time they underwent perfusion-fixation of their brains for pathologic analysis. Of the total, four out of four puppies arrested for 1.0 h exhibited no brain damage, including one recovered for 72 h; whereas one out of three and four out of four puppies arrested for 1.5 and 1.75 h, respectively, showed brain damage predominantly of the cerebral cortex but also of the basal ganglia and amygdaloid nucleus. The hippocampus was spared, even in a 1.75-h-arrested animal which was maintained for 72 h. No differences in pre- or post-arrest systemic blood pressure, heart rate, or acid-base balance were observed between the brain damaged and undamaged animals except for the single damaged animal arrested for 1.5 h, for which the blood pressure prior to cardiac arrest and during recovery was the lowest of all survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Allopurinol administered after inducing hypoxia-ischemia reduces brain injury in 7-day-old rats.

We determined that treatment of immature rats with allopurinol at 15 min after cerebral hypoxia-ischemia reduces brain damage. Seven-d postnatal rats were subjected to right common carotid artery ligation followed by 2.25 h of hypoxia (8% O2). At 15 min of recovery in room air, the rat pups received either allopurinol (135 mg/kg s.c.) or saline. Some of the rats (n = 65) were killed at 42 h of recovery for measurement of cerebral hemispheric water content. Other animals (n = 63) were killed at 30 d for morphologic assessment of the severity of damage. In separate rats, we measured the levels of allopurinol and its metabolites in serum and in the brain around the time of peak serum levels. We also determined the effect of allopurinol on rat pup body temperature. Allopurinol reduced the increase in right hemisphere water content and markedly reduced atrophy. No cavitary lesions were seen in the 31 allopurinol-treated rats, whereas 15 of 32 saline-treated rats had cavitary cerebral lesions. Histologic examination confirmed that the allopurinol-treated rats had less brain injury. Serum allopurinol and oxypurinol peaked between 0.5 and 1 h after allopurinol injection. Their peak serum concentrations at 0.75 h postinjection combined was between 360 and 510 microM. Allopurinol did not lower rectal temperature more than 0.04 degrees C. In conclusion, high-dose allopurinol administered at 15 min of recovery from cerebral hypoxia-ischemia markedly reduces both acute brain edema and long-term cerebral injury in immature rats.

Allopurinol↗
PubMed1993

Influence of mild hypothermia on hypoxic-ischemic brain damage in the immature rat.

Recent studies in adult animals have shown that even small decreases in brain or core temperature ameliorate the damage resulting from hypoxic-ischemic insults. To determine the effect of minor reductions in ambient temperature either during or after an hypoxic-ischemic insult on the brain of the immature rat, 7-d-postnatal rat pups underwent unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 3 h. Control animals were maintained at 37 degrees C during hypoxia-ischemia. Intraischemic hypothermia was induced during the insult at temperatures of 34 degrees C and 31 degrees C. Postischemic hypothermia was induced by exposing rat pups that underwent hypoxia at 37 degrees C to recovering environments of 34 degrees C and 31 degrees C. Temperatures were recorded every 15 min from thermistor probes placed in the ipsilateral hemisphere and rectally. Neuropathologic alterations were assessed at 30 postnatal d. During hypoxia, animals became poikilothermic. Brain damage occurred in 90% of rat pups exposed to hypoxia-ischemia at 37 degrees C. Cerebral injury significantly decreased with decreasing temperatures during hypoxia-ischemia (p < 0.01). Only 30% of rats had brain damage when exposed to hypoxia-ischemia at 34 degrees C, and none of the rats exposed at 31 degrees C had brain damage. In contrast, there was no difference in the extent of cerebral injury between rat pups recovered under hypothermic conditions of either 34 degrees C or 31 degrees C compared with those recovered at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Necrotizing infundibulo-hypophysitis: a unique syndrome of diabetes insipidus and hypopituitarism.

Clinical, radiological, histological, and anatomical features in 2 patients with necrotizing infundibulo-hypophysitis are reported. The patients presented with a combination of diabetes insipidus and hypopituitarism. Each was found to have a sellar mass lesion with an abnormally thickened enlarged pituitary stalk that intensively enhanced on contrast magnetic resonance imaging. They were suspected to have pituitary tumors with suprasellar extension. However, tissue obtained at transphenoidal surgery revealed necrosis, fibrosis, and chronic inflammation; there was no evidence of infiltrative, infective, or neoplastic disease processes. Postoperatively, they continued to have diabetes insipidus and hypopituitarism despite radiological improvement and steroid therapy. Several clinical and anatomical features distinguish these 2 cases from classical lymphocytic hypophysitis, the most common entity in the differential diagnosis. Specifically, diabetes insipidus has not been observed preoperatively in 30 cases of lymphocytic hypophysitis, but was present in the 2 cases reported. Histological evidence of tissue necrosis present in these 2 cases is not a feature of lymphocytic hypophysitis. Pituitary stalk involvement on magnetic resonance imaging or computed tomographic scan present in these 2 cases is highly unusual in lymphocytic hypophysitis. Finally, 29 of 30 cases of lymphocytic hypophysitis were females, whereas the 2 cases reported are men. On the basis of these disparate findings, we suggest that these 2 cases represent a unique syndrome, which may be recognized clinically and radiologically.

Adult↗