Search PubMed⌕ Search

Biomedical subjects

B J Crain

Publications and source records attributed to B J Crain.

At least 55 records · Page 3Linked to original sources
PubMed1991

Pulsatile reperfusion after cardiac arrest improves neurologic outcome.

Cardiopulmonary bypass (CPB) using nonpulsatile flow (NPF) is advocated for refractory cardiac arrest. This study examined cerebral outcome after resuscitation with pulsatile flow (PF) versus NPF. Dogs arrested for 12.5 minute were reperfused with NPF (n = 11) using roller pump CPB or PF (n = 11) using mechanical biventricular cardiac massage. Pump flows were similar between groups; however early arterial pressures were greater during PF versus NPF, *p less than 0.05. Circulatory support was weaned at 60 minutes' reperfusion. Neurologic recovery of survivors (n = 16) was significantly better after PF versus NPF, *p = 0.01. The presence of brain lesions on magnetic resonance images did not significantly differ between groups at 7 days. Brain then were removed and regions examined for ischemic changes. Loss of CA1 pyramidal neurons was more severe after NPF versus PF, +p = 0.009. Ischemic changes were more frequent after NPF in the caudate nucleus (+p = 0.009) and watershed regions of the cerebral cortex (+p = 0.062), compared with PF. These results demonstrate that PF improves cerebral resuscitation when treating cardiac arrest with mechanical circulatory support (* = MANOVA with repeated measures, + = categorical data analysis.

Analysis of Variance↗
PubMed1991

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease.

The Neuropathology Task Force of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed a practical and standardized neuropathology protocol for the postmortem assessment of dementia and control subjects. The protocol provides neuropathologic definitions of such terms as "definite Alzheimer's disease" (AD), "probable AD," "possible AD," and "normal brain" to indicate levels of diagnostic certainty, reduce subjective interpretation, and assure common language. To pretest the protocol, neuropathologists from 15 participating centers entered information on autopsy brains from 142 demented patients clinically diagnosed as probable AD and on eight nondemented patients. Eighty-four percent of the dementia cases fulfilled CERAD neuropathologic criteria for definite AD. As increasingly large numbers of prospectively studied dementia and control subjects are autopsied, the CERAD neuropathology protocol will help to refine diagnostic criteria, assess overlapping pathology, and lead to a better understanding of early subclinical changes of AD and normal aging.

Aged↗
PubMed1991

Increased AMPA-sensitive quisqualate receptor binding and reduced NMDA receptor binding in epileptic human hippocampus.

Based on results from the kindling model of epilepsy, we hypothesized that enhanced binding of radioligands to the NMDA receptor and decreased binding to the alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA)-sensitive quisqualate (ASQ) receptor would be found within epileptic hippocampi of humans with complex partial epilepsy (CPE). To test these hypotheses, we used tissue that was surgically removed from patients with intractable CPE, and control tissue that was obtained at autopsy. We used autoradiographic techniques to measure ASQ receptor binding (with 3H-AMPA as the radioligand) and binding to 2 sites on the NMDA receptor/channel complex: the agonist recognition site (with 3H-glutamate) and the phencyclidine (PCP) binding site that resides within the NMDA channel [with 3H-N-(1-[thienyl]cyclohexyl) piperidine (TCP) in the presence of saturating concentrations of NMDA and glycine]. Measurements of receptor binding were corrected for pathologic alterations in neuronal density. Contrary to our expectations, ASQ receptor binding was significantly increased (100%; p less than 0.02) in the dentate gyrus stratum moleculare in patients with CPE (n = 8), and it was unchanged in other hippocampal regions. In nearby sections from the same specimens, binding was significantly decreased to the agonist recognition site of the NMDA receptor in the stratum oriens of area CA3 (46%; p less than 0.05) and was also decreased to the PCP site in the stratum radiatum and stratum oriens of CA3 (44% and 74%, respectively; p less than 0.05). The increase in ASQ receptor binding may contribute to hyperexcitability in these epileptic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Effects of transient forebrain ischemia in area CA1 of the gerbil hippocampus: an in vitro study.

Selective delayed post-ischemic degeneration of CA1b neurons takes place in tissue slices in vitro as it does in brain in situ. Therefore neither selectivity nor the delay of the process can be explained by vascular factors. Changes of orthodromic evoked potentials precede morphologic signs of degeneration, but antidromic activation of neurons fails pari passu with histopathologic degeneration. The marked, transient, enhancement of excitatory synaptic potentials is compatible with the idea that increased release of excitatory amino acids contributes to neuron damage. The fact that degeneration proceeds in the absence of spontaneous activity or overt electrographic seizures indicates, however, that increased excitation cannot be the sole cause of the damage. Postsynaptic excitability of neurons decreases even while synaptic potentials are enhanced. The mechanism of decreased excitability is not clear, but its development could be interpreted as a compensatory change, counteracting enhanced excitatory transmission. We confirmed that it is possible to save neurons by drug treatment administered after the ischemic insult, and demonstrated that such protection is not due to an effect on blood vessels. These findings are relevant to the proposed clinical use of NMDA receptor antagonists to prevent ischemic brain damage (Meldrum, 1985; Rothman and Olney, 1986; Choi, 1988).

Animals↗
PubMed1990

Electron microscopic study of the gerbil dentate gyrus after transient forebrain ischemia.

Silver impregnation performed 1-2 days after transient forebrain ischemia in the Mongolian gerbil demonstrated terminal-like granular deposits in the outer two-thirds of the hippocampal dentate molecular layer (perforant path terminal zone), even though neither the cell bodies of origin of the perforant path nor the dentate granule cells were destroyed. Electron microscopic studies of the dentate gyrus were performed in an effort to discover the identity of these degenerating structures. Electron microscopy revealed that the granular silver deposits corresponded to electron-dense profiles. Many of these were degenerating boutons and some were degenerating postsynaptic dendritic fragments, but most of them could not be identified with certainty. Electron-dense profiles were less numerous than expected from the density of granular silver deposits. These structures were probably the degenerating axons, axon terminals and dendrites of CA4 neurons. The granular silver deposits and electron-dense boutons observed in the inner third of the dentate molecular layer 5 days after transient ischemia can probably be explained by the ischemia-induced degeneration of CA4 mossy cells, which give rise to the dentate associational-commissural projection. Finally, most mossy fiber boutons in area CA4 and some boutons in the molecular layer appeared watery and enlarged on postischemia days 1 and 2. Mossy fiber boutons with this ultrastructural appearance have previously been observed in seizure-prone animals and in animals undergoing convulsant-induced seizures. Although no postischemic seizures occur under the conditions of this study, these findings support the idea that excitatory pathways become hyperactive after transient ischemia.

Animals↗
PubMed1990

A simple, inexpensive method of monitoring brain temperature in conscious rodents.

A method was developed to monitor brain temperature in conscious, unrestrained rodents. A commercially available thermocouple microprobe was modified so that it could be screwed firmly into a guide cannula that had been stereotactically implanted in the brain. Because the microprobe remains firmly in place, it is possible to record continuously for several hours from a single animal. Because the microprobe is easily removed, one can also record intermittently from several animals at once. The necessary equipment is relatively inexpensive and the modified microprobe can be sterilized and reused indefinitely. This method has proved especially useful for monitoring brain temperature during and after transient cerebral ischemia, an insult that destroys CNS neurons in a temperature-sensitive fashion.

Animals↗
PubMed1990

Selective neocortical and thalamic cell death in the gerbil after transient ischemia.

In animal models of transients ischemia, selective vulnerability and delayed neuronal death in the hippocampus have been extensively described. However, little is known about selective damage in the neocortex and the thalamus, even though deficits in sensorimotor function are common in humans surviving hypoxic/ischemic episodes. This study investigated the neurodegenerative effects of transient ischemia in the gerbil neocortex and thalamus with use of Cresyl Violet and silver impregnation staining methods. In addition, immunohistochemistry of an astrocyte-associated protein, glial fibrillary acidic protein, was used to assess the astrocytic response to ischemia. Pyramidal cells in layers 3 and 6 of somatosensory and auditory cortex were exceptionally sensitive to ischemia, whereas the neurons in layers 2, 4 and 5 were more resistant to ischemia. More pyramidal cells were killed in layer 3 than in layer 6. This bilaminar pattern of neuronal death developed after periods of ischemia ranging from 3 to 10 min and was identifiable at post-ischemic survival times of 6 h to one month. Somatodendritic argyrophilia in the neocortex was identified as early as 6-12 h after 5 min of ischemia. The greatest number of degenerating cortical neurons were stained two to four days after ischemia. With 10 min of ischemia, argyrophilic neurites and neurons were also found as early as 8 h after the occlusion. The most extensive damage was noted in the ventroposterior nucleus, the medial geniculate nucleus, and the intralaminar nuclei two to four days after ischemia. Thus, selective vulnerability and delayed neuronal death are evident in both the neocortex and the thalamus after transient ischemia. These regions need to be examined when considering the efficacy of potential neuroprotective drugs.

Animals↗
PubMed1990

Regulatory changes in presynaptic cholinergic function assessed in rapid autopsy material from patients with Alzheimer disease: implications for etiology and therapy.

Brain regions from patients with or without Alzheimer disease (AD) were obtained within 2 hr of death and examined for indices of presynaptic cholinergic function. Consistent with loss of cholinergic projections, cerebral cortical areas involved in AD exhibited decreased choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6) activity. However, remaining nerve terminals in these regions displayed marked up-regulation of synaptosomal high affinity [3H]choline uptake, a result indicative of relative cholinergic hyperactivity. As choline uptake is also rate-limiting in acetylcholine biosynthesis, these findings have implications for both therapy and identification of causes contributing to neuronal death in AD.

Alzheimer Disease↗
PubMed1990

MR imaging in patients with temporal lobe seizures: correlation of results with pathologic findings.

Thirty-nine consecutive patients with medically intractable complex partial seizures were studied with electroencephalography and MR imaging to localize an epileptogenic focus for temporal lobectomy. The patients were divided into three groups on the basis of pathologic findings after lobectomy: Group 1 comprised 13 patients with neoplasms, hamartomas, or cysts; group 2 comprised 13 patients with moderate and severe mesial temporal sclerosis (one patient was included in both groups 1 and 2); and group 3 comprised 14 patients who underwent aspiration lobectomy, which yielded limited tissue for pathologic study so no pathologic diagnosis was made. The majority of the patients in group 3 were assumed to have mesial temporal sclerosis. Abnormal MR signal in the temporal lobe on T2-weighted images was graded as minimal increase (1+), intermediate or moderate increase (2+), and very significant increase (3+). An abnormal signal was demonstrated in 26 (67%) of the 39 patients. In group 1, the tumor/cyst subgroup, an abnormal signal was seen in all 13 patients. Most had 3+ signal. There was increased signal in eight (62%) of 13 patients in group 2 and in six (43%) of 14 patients in group 3. This study suggests that MR can detect almost all tumors and a significant number of mesial temporal sclerosis lesions in individuals with complex partial seizures. On the basis of this small series, individuals who exhibit significant signal (3+) can be expected to have neoplasms, hamartomas, or cysts, and patients who exhibit minimal signal (1+) will usually have mesial temporal sclerosis.

Adult↗
PubMed1990

Postischemic synaptic excitation and N-methyl-D-aspartate receptor activation in gerbils.

Transient forebrain ischemia leads to the delayed degeneration of CA1b hippocampal pyramidal cells. In previous studies using the gerbil carotid occlusion model, we demonstrated that CA1b pyramidal cell degeneration is preceded by a period of enhanced excitatory transmission. Experiments with hippocampal slices prepared after 5 minutes of bilateral carotid artery occlusion show that ischemia enhances excitatory synaptic transmission and reduces pyramidal cell excitability before it abolishes synaptic function. In the present study, we tested the hypothesis that these effects require the activation of N-methyl-D-aspartate receptors during the postischemic period. Hippocampal slices were prepared 20-30 minutes after carotid occlusion, and Schaffer collateral-commissural input-output curves were constructed from recordings made every 30-60 minutes for 11-14 hours. Inclusion of the selective, reversible N-methyl-D-aspartate receptor antagonist 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid in the superfusion medium completely prevented the progressive loss of pyramidal cell excitability that normally follows this ischemic insult. This antagonist also prevented the postischemic increases in the duration and initial slope of the focally-recorded excitatory postsynaptic potential. The antagonist could still partially block the effects of transient forebrain ischemia when treatment was delayed for 4 hours. Our results confirm that the deleterious electrophysiologic changes in area CA1b depend on the continuing activation of N-methyl-D-aspartate receptors. Delayed ischemic neuronal death may result, in part, from excessive synaptic excitation during the postischemic period. However, other factors that are eliminated by preparing hippocampal slices appear to play an important role as well.

Animals↗
PubMed1990

Neuroendocrine carcinoma of the oral cavity.

We report the clinical and pathologic features of a small cell neuroendocrine carcinoma arising in the oral cavity of a 63-year-old man. The tumor stained positively with neuron-specific enolase and had dense core granules ultrastructurally. Chemotherapy ordinarily given for pulmonary small cell carcinoma induced a clinical remission. When the tumor recurred 8 mo later, focal squamous differentiation was present within the neuroendocrine carcinoma. The patient died 2.5 yr after presentation.

Carcinoma, Small Cell↗
PubMed1989

Absence of electrographic seizures after transient forebrain ischemia in the Mongolian gerbil.

EEG was continuously recorded from Mongolian gerbils for 4 days after transient bilateral forebrain ischemia, to determine whether ischemic brain damage in this species is necessarily associated with seizures. Gerbils were chronically implanted with EEG recording electrodes in hippocampal area CA1, striatum and frontal neocortex and were subjected to a 5-10 min occlusion of both common carotid arteries. During the first few hours after the occlusion, the EEG was dominated by slow waves similar to those recorded from human brain after a damaging episode of cerebral ischemia. Amplitudes of the hippocampal and striatal EEG declined markedly with time, presumably as a result of neuronal degeneration. Ictal activity was never recorded, even from animals that suffered extreme damage to the hippocampal formation and striatum. Therefore ischemic brain damage in the gerbil does not result from seizure activity.

Animals↗
PubMed1989

Lesions of excitatory pathways reduce hippocampal cell death after transient forebrain ischemia in the gerbil.

Transient forebrain ischemia produces a spatially and temporally selective pattern of neuronal degeneration in the hippocampal formation of the Mongolian gerbil. Ischemic neuronal death has been suggested to depend on the activation of excitatory hippocampal pathways that project to the vulnerable neurons. This idea was tested by examining the effect of a unilateral entorhinal cortical lesion or a unilateral knife cut lesion of intrahippocampal pathways on the neuropathology produced by 5 min of complete forebrain ischemia. A prior lesion of either the ipsilateral entorhinal cortex or the mossy fiber and Schaffer collateral-commissural pathways partially prevented the destruction of CA1b pyramidal cells in most animals. It did not, however, reduce the extent of ischemic neuronal death in any other hippocampal subfield. Within area CA1b, an entorhinal lesion protected an average of 23% of the pyramidal cells and a transection of both mossy and Schaffer collateral-commissural fibers protected an average of 36.5%. CA1b pyramidal cells saved from ischemia-induced degeneration appeared clearly abnormal when stained with cresyl violet or by silver impregnation. It is suggested that lesions of excitatory pathways attenuate ischemic damage to area CA1b by directly or indirectly reducing the level of synaptic excitation onto the vulnerable neurons. However, only a relatively small percentage of hippocampal neurons can be protected by these lesions in the gerbil ischemia model and there is reason to believe that the neurons protected in this manner may not be electrophysiologically competent. Synaptic excitation therefore appears to play an important, but not an essential, role in this model of ischemic brain damage.

Afferent Pathways↗
PubMed1989

Postischemic synaptic physiology in area CA1 of the gerbil hippocampus studied in vitro.

After transient forebrain ischemia in the Mongolian gerbil, CA1b hippocampal pyramidal cells degenerate during a period of 2-4 d. We tested the hypothesis that this delayed neuronal death is preceded by excessive synaptic excitation. Hippocampal slices were prepared from gerbils that had been subjected to a 5 min occlusion of both common carotid arteries. Input/output curves demonstrated enhancement of the initial slope of the Schaffer collateral-commissural focally recorded EPSP at all stimulus currents between 5 and 10 hr after the ischemic insult. The duration of the focally recorded EPSP also increased. At the same time, the excitability of the CA1b pyramidal cells decreased. Thus, the EPSP brought fewer pyramidal cells to threshold than the same size EPSP in control slices. During the first 14 hr after ischemia, the antidromic population spike remained unaffected. By 24 hr after ischemia, however, the focally recorded EPSP and both orthodromic and antidromic population spikes were markedly depressed, and they declined further over the next 2 d. No recovery was detected. In the same slices, transient ischemia only mildly and reversibly affected the response of dentate granule cells to perforant path stimulation and did not affect their response to antidromic stimulation. Hippocampal slices adjacent to those used for electrophysiological recording were analyzed histologically. Examination of somatic argyrophilia confirmed that CA1b pyramidal cells suffered delayed neuronal death, whereas dentate granule cells remained intact. Pyramidal cell argyrophilia was, however, not detected until 2 d after these neurons had become virtually inexcitable. We conclude that CA1b pyramidal cells begin to lose electrophysiological function well before definite morphological signs of degeneration become visible. The observation of enhanced excitatory transmission 5-10 hr after reperfusion is consistent with the idea that delayed ischemic neuronal death results, at least in part, from excessive excitation.

Action Potentials↗