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Biomedical subjects

D G Fujikawa

Publications and source records attributed to D G Fujikawa.

29 records · Page 2Linked to original sources
PubMed1989

Posthypoxic treatment with MK-801 reduces hypoxic-ischemic damage in the neonatal rat.

We evaluated the neuroprotective effect of MK-801, a noncompetitive, selective N-methyl-D-aspartate receptor antagonist, in a neonatal hypoxic-ischemic animal model. Seven-day-old rats underwent bilateral ligation of the carotid arteries followed by exposure to an 8% oxygen atmosphere for 1 hr. We sacrificed the animals 72 hrs later and assessed the hypoxic-ischemic brain damage histologically. MK-801 (10 mg/kg), administered IP 0.5 hr before the hypoxia, completely prevented hypoxic-ischemic infarction in cerebral cortex, while treatment immediately and 1 hr after the end of the hypoxia resulted in 76% and 52% reduction in the infarcted area, respectively. MK-801, given 0.5 hr before and immediately after the insult, reduced striatal damage and, given 0.5 hr before, attenuated neuronal necrosis in hippocampal regions. These results show that in neonates MK-801 is neuroprotective even when administered up to 1 hr after the end of a hypoxic-ischemic insult.

Animals↗
PubMed1988

Generalized seizures deplete brain energy reserves in normoxemic newborn monkeys.

The cerebral metabolic response to bicuculline (BC)-induced status epilepticus (SE) was studied in two-week-old ketamine-anesthetized marmoset monkeys. During 30-min clonic seizures, mean blood pressure, plasma glucose and paO2 did not decrease and plasma lactate doubled. Brains were funnel-frozen and punch biopsies of frontoparietal cortex, temporal cortex and thalamus were analyzed for ATP, phosphocreatine (PCr), glucose and lactate. There were marked reductions of ATP (to 56-77% of controls), PCr (to 23-28% of controls) and glucose (to 1-4% of controls), and lactate increased 3- to 6-fold in seizure animals. NADH fluorescence increased during seizures in cerebral cortex, thalamus, amygdaloid nuclei, hippocampus, posterior striatum and hemispheric white matter. This suggests a reduced tissue redox state in these regions and is correlated with the high energy phosphate depletion and elevated lactate in cortex and thalamus. Our results demonstrate a significant depletion of energy reserves and glucose in cerebral cortex and thalamus during neonatal seizures in the absence of adverse systemic factors. These seizure-induced metabolic changes in brain could have adverse long-term effects on brain development and function.

Adenosine Triphosphate↗
PubMed1988

Cerebral hypoxia-ischemia in immature rats: methodological considerations.

We used a model of perinatal hypoxic/ischemic brain damage which combines unilateral common carotid artery ligation and hypoxia (8% O2). Protein synthesis inhibition and cell loss were found in the ipsilateral forebrain of 11-day-old rats when hypoxia was initiated 4 h but not 24 h after carotid ligation. [14C]Iodoantipyrine uptake studies suggest that compensating vascular changes which protect the ipsilateral forebrain occur within 24 h of carotid ligation.

Animals↗
PubMed1988

Low [3H]cytochalasin B binding in the cerebral cortex of newborn rat.

The concentrations of glucose transporter in the cerebral cortex and brainstem of neonatal (4-7 days old) and adult rats were measured using [3H]cytochalasin B binding. There was significantly lower binding in neonatal cortex (1.9 +/- 0.7 pmol/mg protein) compared to adult (8.9 +/- 2.5 pmol/mg protein). Scatchard analysis indicates this difference is due to a lower Bmax (neonate, 9.7 pmol/mg protein; adult, 18.6 +/- 1.3 pmol/mg protein). Measurement of [3H]cytochalasin B binding in microvessels prepared from cortex of adult (28.1 +/- 3.5 pmol/mg protein) and neonate (12.8 +/- 1.9 pmol/mg protein) indicates a lower binding in the microvasculature of neonates, whereas no such difference was seen in the binding in microvessels prepared from adult and neonatal brainstem (adult, 11.8 +/- 2.3 pmol/mg protein; neonate, 9.4 +/- 2.7 pmol/mg protein). In both adult and neonate brain, there is an enrichment of glucose transporters in the microvasculature.

Aging↗
PubMed1986

Preferential blood flow to brainstem during generalized seizures in the newborn marmoset monkey.

The effect of generalized seizures on local cerebral blood flow was studied autoradiographically in 21 immature marmoset monkeys, using either [123I]- or [131I]isopropyliodoamphetamine. Generalized convulsions were induced in ketamine-anesthetized and awake monkeys with bicuculline and continued for 4-59 min. During convulsions in marmosets less than 3 weeks of age, there was a striking rearrangement of blood flow in favor of the brainstem pontomedullary region. The ratios of blood flow in pons-medulla to blood flow in cerebral cortex, putamen, ventroposterior thalamic nuclei, lateral geniculate nuclei, cerebellum and hemispheric white matter increased 1 1/2 to 2 times compared to controls. In seizure animals 4-8 weeks of age, the redistribution of blood flow to brainstem did not occur. Although metabolic acidosis developed after 30 min of bicuculline-induced seizures, mean arterial blood pressure, temperature, arterial pO2 and pCO2 did not differ significantly from controls, indicating that hypoxemia, hypercapnia and hypotension cannot explain the altered cerebral blood flow pattern. The redistribution phenomenon could be explained by more pronounced vasodilatation in brainstem than many other brain regions during generalized seizures in newborn monkeys. Lack of significant vasodilatation in forebrain structures such as cerebral cortex could contribute to neuronal damage by limiting substrate supply at a time of increased metabolic activity.

Amphetamines↗
PubMed1986

Metabolic anatomy of generalized bicuculline seizures in the newborn marmoset monkey.

Sustained convulsive seizures were induced with bicuculline in ketamine-anesthetized marmoset monkeys aged 7 to 18 days. Relative 2-deoxyglucose metabolism was compared in convulsing (N = 9) and control (N = 6) animals. Convulsions were accompanied by striking focal increases in cerebral 2-deoxyglucose uptake which were remarkably consistent from animal to animal. Increased 2-deoxyglucose uptake in broad cortical regions (2- to 3-fold) suggests that cortical mechanisms can be important, even in neonatal seizures. The hippocampus and other limbic system structures were markedly activated, as were nuclei of the basal ganglia and thalamus. In contrast, sensory systems were less affected. No increase in 2-deoxyglucose uptake was found in the lateral geniculate nuclei, and a 22% decrease was found in the inferior colliculus (central core). Increased uptake was found in several white matter regions, and activation of the corpus callosum (2.6-fold) was comparable to that found for many gray matter regions. Our results show that generalized bicuculline seizures can produce striking focal increases in cerebral 2-deoxyglucose metabolism in brain regions known to be vulnerable to epileptic brain damage.

Animals↗
PubMed1986

Brain protein metabolism in epilepsy.

Both generalized and focal seizures dissociate brain polyribosomes and severely inhibit brain protein synthesis. This effect is found in freely convulsing animals and in animals that have been paralyzed and oxygen-ventilated in order to prevent hypoxemia, cerebral hypoxia, and other systemic changes associated with convulsions. Recent autoradiographic studies have shown that generalized seizures can result in striking focal inhibition of brain protein synthesis in adult rats and newborn marmoset monkeys. Local cerebral glucose metabolism and local cerebral blood flow were also studied in newborn marmosets by autoradiography. Although flow and metabolism are closely matched in control marmosets, seizures result in large local increases in 2-deoxyglucose metabolism, with lesser or no increases in local cerebral blood flow resulting in a relative mismatch. Those regions in which protein synthesis was most severely inhibited were those in which the relative mismatch between blood flow and metabolism was most marked. The molecular mechanisms regulating protein biosynthesis are not known. Translational regulation during seizures appears to be exerted, in large part, at the initiation step. A likely mechanism is the inhibition of ternary complex formation, one of the early steps in the initiation process, by increases in the intracellular ratio of [GDP]:[GTP]. This ratio is related to the cells' energy charge. Reduced levels of ATP during seizures can lead to an increased ratio of [GDP]:[GTP] via of the enzyme nucleoside diphosphate kinase (E.C. 2.7.4.6) and to inhibition of protein synthesis initiation. Regulation of protein biosynthesis during seizures is likely to be complex and exerted at many sites; some of these possibilities are discussed.

Acid-Base Equilibrium↗
PubMed1982

Phaeohyphomycosis of brain: granulomatous encephalitis caused by Drechslera spicifera.

Drechslera spicifera is a dematiaceous fungus which occurs widely in nature but only rarely has been implicated in animal and human infections. Previous infections have occurred in superficial and subcutaneous sites or were encountered in immunologically compromised hosts. This report documents a case of granulomatous encephalitis due to Drechslera spicifera in an immunologically competent woman with no known underlying disease, from whom the fungus was isolated. Animal pathogenicity studies in mice reproduced the histopathologic features, and the fungus was reisolated from the animals.

Adult↗
PubMedDate not supplied

The effects of adrenergic, opioid and pancreatic polypeptidergic compounds on feeding and other behaviors in neonatal leghorn chicks.

The present study examined the effects of intracerebral (IC) administration of pancreatic polypeptide (PP), neuropeptide Y (NPY), norepinephrine (NE), dynorphin and naloxone on food intake in 2-day-old Leghorn chicks. Of the compounds studied, only PP (20 micrograms) and naloxone (10 and 20 micrograms) elevated food intake significantly as compared to saline injections. NPY, a potent orexigenic agent in mammals, did not elevate consumption significantly in a dose-related fashion. This latter finding was attributed to the occurrence of tonic-clonic convulsions following NPY administration. However, for those chicks which did not exhibit behavioral convulsions, food intake appeared to be elevated by 1, 5 and 10 micrograms of NPY. Similarly, NE did not elevate food intake but instead induced sedation and narcolepsy, a behavioral response which could be distinguished from the convulsions observed after NPY. In a separate group of chicks, the effect of NPY on cortical activity was examined. Bipolar electrodes were used to record EEG activity before and after IC injections of saline, NPY or NE. The behavioral convulsions induced by NPY corresponded with an increase in high amplitude sharp-wave activity, which persisted for up to 30 min post-injection. Collectively, these results suggest that the neurochemical substrates for feeding in 2-day-old Leghorn chicks are distinct from those underlying food intake in adult mammals.

Animals↗
PubMedDate not supplied

Clinical characterization of Alzheimer's disease: reliability of 'age at onset' and a new descriptor, 'age at shift'.

To determine the interrater reliability of clinical descriptors for Alzheimer's disease (AD), we assessed the degree of agreement among four clinicians who rated 21 patients during a longitudinal study. Despite variability in response patterns, degree of agreement for determining age at onset of dementia was statistically significant (P less than 0.005). We also found significant agreement (P less than 0.0001) among three clinicians for the clinical descriptor, "age at shift" from questionable to probable AD, according to the National Institutes of Health Consensus Criteria. These data demonstrate that both retrospective and prospective descriptors can be reliably determined in the clinical assessment of AD.

Age Factors↗