scholarly journals Chronic Dexamethasone Pretreatment Aggravates Ischemic Neuronal Necrosis

1986 ◽  
Vol 6 (4) ◽  
pp. 395-404 ◽  
Author(s):  
Tohru Koide ◽  
Tadeusz W. Wieloch ◽  
Bo K. Siesjö
Keyword(s):  
Brain Damage ◽  
Glucocorticoid Receptors ◽  
Neuronal Damage ◽  
Energy Charge ◽  
Cyclooxygenase Inhibitors ◽  
Brain Areas ◽  
Neuronal Necrosis ◽  
Brain Glucose ◽  
Glucose Levels ◽  
The Brain

This study addresses the question of whether the cyclooxygenase inhibitors indomethacin and diclofenac and the glucocorticosteroid dexamethasone ameliorate neuronal necrosis following cerebral ischemia. In addition, since these drugs inhibit the production of prostaglandins and depress phospholipase A2 activity, respectively, the importance of free fatty acids (FFAs) on the development of ischemic neuronal damage was assessed. Neuronal damage was determined in the rat brain at 1 week following 10 min of forebrain ischemia. The cyclooxygenase inhibitors, whether given before or after ischemia, failed to alter the brain damage incurred. Animals given dexamethasone were divided into three groups and the drug was administered at a constant dosage of 2 mg/kg: (a) 2 days, 1 day, and 3 h intraperitoneally before (chronic pretreatment), (b) 3 h intraperitoneally before (acute pretreatment), and (c) 5 min intravenously and 6 h and 1 day intraperitoneally after (chronic posttreatment) induction of ischemia. Acute pretreatment did not affect the histopathological outcome. Chronic posttreatment of animals with dexamethasone ameliorated the damage inflicted on the caudate nucleus, but had no effect on other brain areas investigated. Unexpectedly, the chronic pretreatment aggravated the brain damage and caused seizures following ischemia. Histopathological data showed massive neuronal damage in these brains. The accumulation of FFA levels during ischemia was markedly suppressed, and the decrease in the energy charge was curtailed by chronic pretreatment with dexamethasone. However, brain glucose levels in control animals and lactic acid concentrations following 10 min of ischemia were significantly higher both in the cerebral cortex and in the hippocampus of dexamethasone-treated animals. These results suggest that aggravation of neuronal necrosis by chronic dexamethasone pretreatment could be ascribed to lactic acidosis due to hyperglycemia in combination with an action of dexamethasone on glucocorticoid receptors in the brain.

Aetiologies and anatomy of confabulation

2017 ◽  
Author(s):  
Armin Schnider
Keyword(s):  
Brain Damage ◽  
Limbic Encephalitis ◽  
Artery Aneurysm ◽  
Anterior Communicating Artery ◽  
Brain Areas ◽  
Anatomical Basis ◽  
Korsakoff Syndrome ◽  
Hypoxic Brain ◽  
Degenerative Dementia ◽  
The Brain

What diseases cause confabulations and which are the brain areas whose damage is responsible? This chapter reviews the causes, both historic and present, of confabulations and deduces the anatomo-clinical relationships for the four forms of confabulation in the following disorders: alcoholic Korsakoff syndrome, traumatic brain injury, rupture of an anterior communicating artery aneurysm, posterior circulation stroke, herpes and limbic encephalitis, hypoxic brain damage, degenerative dementia, tumours, schizophrenia, and syphilis. Overall, clinically relevant confabulation is rare. Some aetiologies have become more important over time, others have virtually disappeared. While confabulations seem to be more frequent after anterior brain damage, only one form has a distinct anatomical basis.

scholarly journals Antecedent glycemic control reduces severe hypoglycemia-induced neuronal damage in diabetic rats

2013 ◽  
Vol 304 (12) ◽  
pp. E1331-E1337 ◽  
Author(s):  
Candace M. Reno ◽  
Tariq Tanoli ◽  
Adam Bree ◽  
Dorit Daphna-Iken ◽  
Chen Cui ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Brain Damage ◽  
Insulin Treatment ◽  
Neuronal Damage ◽  
Blood Glucose Control ◽  
Severe Hypoglycemia ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Sprague Dawley Rats

Brain damage due to severe hypoglycemia occurs in insulin-treated people with diabetes. This study tests the hypothesis that chronic insulin therapy that normalizes elevated blood glucose in diabetic rats would be neuroprotective against brain damage induced by an acute episode of severe hypoglycemia. Male Sprague-Dawley rats were split into three groups: 1) control, non-diabetic; 2) STZ-diabetic; and 3) insulin-treated STZ-diabetic. After 3 wk of chronic treatment, unrestrained awake rats underwent acute hyperinsulinemic severe hypoglycemic (10–15 mg/dl) clamps for 1 h. Rats were subsequently analyzed for brain damage and cognitive function. Severe hypoglycemia induced 15-fold more neuronal damage in STZ-diabetic rats compared with nondiabetic rats. Chronic insulin treatment of diabetic rats, which nearly normalized glucose levels, markedly reduced neuronal damage induced by severe hypoglycemia. Fortunately, no cognitive defects associated with the hypoglycemia-induced brain damage were observed in any group. In conclusion, antecedent blood glucose control represents a major modifiable therapeutic intervention that can afford diabetic subjects neuroprotection against severe hypoglycemia-induced brain damage.

scholarly journals Brain Glucose Levels in Portacaval-Shunted Rats with Chronic, Moderate Hyperammonemia: Implications for Determination of Local Cerebral Glucose Utilization

1994 ◽  
Vol 14 (1) ◽  
pp. 113-124 ◽  
Author(s):  
Nancy F. Cruz ◽  
Gerald A. Dienel
Keyword(s):  
Glucose Utilization ◽  
Normal Values ◽  
Brain Structures ◽  
Glucose Content ◽  
Brain Glucose ◽  
Glucose Levels ◽  
Lumped Constant ◽  
Dg Method ◽  
The Brain

Rates of glucose utilization (lCMRglc) in many structures of the brain of fed, portacaval-shunted rats, when assayed with the [14C]deoxyglucose (DG) method in our laboratory, were previously found to be unchanged (30 of 36 structures) or depressed (6 structures) during the first 4 weeks after shunting, but to rise progressively to higher than normal values in 25 of 36 structures from 4–12 weeks. In contrast, lCMRglc, when assayed with the [14C]glucose method in another laboratory, was depressed in most structures of brains of 4–8-week shunted rats that had relatively high brain ammonia levels. There was a possibility that the increases in lCMRglc obtained with the [14C]DG method may have been artifactual, due, in part, to a change in brain glucose content which could alter the value of the lumped constant of the DG method. Brain glucose levels of shunted rats were, therefore, assayed by both direct chemical measurement in freeze-blown samples and by determination of steady-state brain:plasma distribution ratios for [14C]methylglucose; the methylglucose distribution ratio varies as a function of plasma and tissue glucose contents. Within a week after shunting, ammonia levels in blood and brain rose to 0.25–0.30 m M and 0.35–0.70 μmol/g, respectively, and mean plasma glucose levels fell from 9–10 m M to 7.4–8.5 m M, and then remained nearly constant. Brains of fedshunted rats had normal glycogen levels and stable but moderately reduced glucose contents between 1 and 12 weeks (i.e., 1.9–2.2 μmol/g). [14C]Methylglucose distribution ratios were essentially the same as those in controls in 22 brain structures at 2 and 8 weeks after shunting. Because brain glucose levels remained stable from 1 to 12 weeks after shunting, there is no evidence to support the hypothesis that the value of the lumped constant would have changed and caused an artifactual rise in lCMRglc.

Chronic hypoglycemia increases brain glucose transport

1986 ◽  
Vol 251 (4) ◽  
pp. E442-E447 ◽  
Author(s):  
A. L. McCall ◽  
L. B. Fixman ◽  
N. Fleming ◽  
K. Tornheim ◽  
W. Chick ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Creatine Phosphate ◽  
Regular Insulin ◽  
Diabetic Rats ◽  
Repeated Injection ◽  
Brain Glucose ◽  
Glucose Levels ◽  
Brain Uptake Index ◽  
Acute Hypoglycemia ◽  
The Brain

Glucose transport into the brain is depressed in chronically hyperglycemic (diabetic) rats. To determine whether hypoglycemia has the opposite effect, brain transport of hexoses and other substrates was examined in chronically and acutely hypoglycemic rats. We produced chronic hypoglycemia by implanting insulin-secreting tumors or insulin-releasing osmotic mini-pumps or by repeated injection of protamine zinc insulin (PZI) and acute hypoglycemia by intravascular injection of regular insulin. Blood-brain barrier (BBB) transport was measured using the brain uptake index (BUI) method. In the three models of chronic hypoglycemia, brain glucose extraction was increased compared with controls. The extraction of deoxyglucose and several other hexoses was also increased by chronic hypoglycemia. Acute hypoglycemia had no effect on brain transport. The transport of other substrates was either not affected or depressed, suggesting increased brain hexose transport is specific. Studies of freeze-blown brain in insulinoma-engrafted rats showed that brain glucose levels were depressed while creatine phosphate, ATP, and glucose 6-phosphate were maintained. Tumor removal led to a reversion of brain glucose transport to control rates but only after 5-25 days. These findings support the view that glucose transport across the BBB is modulated by chronic alterations in the ambient glucose concentration. They also may explain why some patients with chronic hypoglycemia tolerate low blood glucose concentrations.

scholarly journals Diabetes increases brain damage caused by severe hypoglycemia

2009 ◽  
Vol 297 (1) ◽  
pp. E194-E201 ◽  
Author(s):  
Adam J. Bree ◽  
Erwin C. Puente ◽  
Dorit Daphna-Iken ◽  
Simon J. Fisher
Keyword(s):  
Brain Damage ◽  
Histological Analysis ◽  
Neuronal Damage ◽  
Severe Hypoglycemia ◽  
Hippocampal Damage ◽  
Sprague Dawley ◽  
Brain Areas ◽  
Sprague Dawley Rats ◽  
Brain Tissue Damage ◽  
Extent Of Damage

Insulin-induced severe hypoglycemia causes brain damage. The hypothesis to be tested was that diabetes portends to more extensive brain tissue damage following an episode of severe hypoglycemia. Nine-week-old male streptozotocin-diabetic (DIAB; n = 10) or vehicle-injected control (CONT; n = 7) Sprague-Dawley rats were subjected to hyperinsulinemic (0.2 U·kg−1·min−1) severe hypoglycemic (10–15 mg/dl) clamps while awake and unrestrained. Groups were precisely matched for depth and duration (1 h) of severe hypoglycemia (CONT 11 ± 0.5 and DIAB 12 ± 0.2 mg/dl, P = not significant). During severe hypoglycemia, an equal number of episodes of seizure-like activity were noted in both groups. One week later, histological analysis demonstrated extensive neuronal damage in regions of the hippocampus, especially in the dentate gyrus and CA1 regions and less so in the CA3 region ( P < 0.05), although total hippocampal damage was not different between groups. However, in the cortex, DIAB rats had significantly (2.3-fold) more dead neurons than CONT rats ( P < 0.05). There was a strong correlation between neuronal damage and the occurrence of seizure-like activity ( r2 > 0.9). Separate studies conducted in groups of diabetic ( n = 5) and nondiabetic ( n = 5) rats not exposed to severe hypoglycemia showed no brain damage. In summary, under the conditions studied, severe hypoglycemia causes brain damage in the cortex and regions within the hippocampus, and the extent of damage is closely correlated to the presence of seizure-like activity in nonanesthetized rats. It is concluded that, in response to insulin-induced severe hypoglycemia, diabetes uniquely increases the vulnerability of specific brain areas to neuronal damage.

scholarly journals Circulating Catecholamines Modulate Ischemic Brain Damage

1986 ◽  
Vol 6 (5) ◽  
pp. 559-565 ◽  
Author(s):  
Tohru Koide ◽  
Tadeusz W. Wieloch ◽  
Bo K. Siesjö
Keyword(s):  
Blood Pressure ◽  
Brain Damage ◽  
Neuronal Damage ◽  
Ischemic Insult ◽  
Ischemic Brain Damage ◽  
Neuronal Necrosis ◽  
Ischemic Brain ◽  
Bilateral Carotid ◽  
Response To Stress ◽  
Bilateral Carotid Artery

In search of factors influencing the outcome of an ischemic insult, we induced 10 min of forebrain ischemia in rats and assessed neuronal necrosis by quantitative histopathology after 1 week of recovery. Procedures for inducing ischemia included bilateral carotid artery clamping and reduction of blood pressure to 40–50 mm Hg by bleeding. To facilitate rapid lowering of blood pressure, a ganglionic blocker, trimethaphan (TMP), was administered at the onset of ischemia. Omission of the ganglionic blocker proved to markedly ameliorate neuronal damage. Similarly favorable effects were obtained when a mixture of adrenaline and noradrenaline (1 μg kg−1 min−1 each) was infused during the early recirculation period in animals previously given TMP. Infusion of noradrenaline alone also ameliorated the damage, though the efficacy was somewhat less. The results suggest that catecholamines, released as a response to stress, ameliorate ischemic brain damage.

Potential pharmacological strategies for the improved treatment of organophosphate-induced neurotoxicity

2014 ◽  
Vol 92 (11) ◽  
pp. 893-911 ◽  
Author(s):  
Shamsherjit Kaur ◽  
Satinderpal Singh ◽  
Karan Singh Chahal ◽  
Atish Prakash
Keyword(s):  
Brain Damage ◽  
Calcium Influx ◽  
Neuronal Damage ◽  
Cholinergic Neurons ◽  
Sensory Deficits ◽  
Neuroprotective Strategies ◽  
Late Stages ◽  
The Brain ◽  
Beneficial Approach ◽  
Cholinergic Projection

Organophosphates (OP) are highly toxic compounds that cause cholinergic neuronal excitotoxicity and dysfunction by irreversible inhibition of acetylcholinesterase, resulting in delayed brain damage. This delayed secondary neuronal destruction, which arises primarily in the cholinergic areas of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, could be largely responsible for persistent profound neuropsychiatric and neurological impairments such as memory, cognitive, mental, emotional, motor, and sensory deficits in the victims of OP poisoning. The therapeutic strategies for reducing neuronal brain damage must adopt a multifunctional approach to the various steps of brain deterioration: (i) standard treatment with atropine and related anticholinergic compounds; (ii) anti-excitotoxic therapies to prevent cerebral edema, blockage of calcium influx, inhibition of apoptosis, and allow for the control of seizure; (iii) neuroprotection by aid of antioxidants and N-methyl-d-aspartate (NMDA) antagonists (multifunctional drug therapy), to inhibit/limit the secondary neuronal damage; and (iv) therapies targeting chronic neuropsychiatric and neurological symptoms. These neuroprotective strategies may prevent secondary neuronal damage in both early and late stages of OP poisoning, and thus may be a beneficial approach to treating the neuropsychological and neuronal impairments resulting from OP toxicity.

scholarly journals The Influence of Mild Body and Brain Hypothermia on Ischemic Brain Damage

1990 ◽  
Vol 10 (3) ◽  
pp. 365-374 ◽  
Author(s):  
Hiroaki Minamisawa ◽  
Carl-Henrik Nordström ◽  
Maj-Lis Smith ◽  
Bo K. Siesjö
Keyword(s):  
Body Temperature ◽  
Brain Damage ◽  
The Body ◽  
Reticular Nucleus ◽  
Temperature Sensitive ◽  
Ischemic Brain Damage ◽  
Neuronal Necrosis ◽  
Ischemic Brain ◽  
Selective Neuronal Vulnerability ◽  
The Brain

The influence of brain and body temperature on ischemic brain damage, notably on the density and distribution of selective neuronal vulnerability, was studied in SPF-Wistar rats subjected to 15 min of forebrain ischemia induced by bilateral occlusion of the common carotid arteries combined with arterial hypotension (50 mm Hg) in a room air environment. In one group of animals, the body temperature was maintained at 37°C but no attempt was made to prevent heat losses from the ischemic brain; i.e., the head was not heated during ischemia. Under those conditions the temperature of the caudoputamen and at a subcutaneous site over the skull bone spontaneously fell to ∼32°C. In four other groups, both the rectal and the subcutaneous skull temperatures were maintained at 38, 37, 35, and 33°C during the ischemia. Our results confirm those recently reported when brain temperature was varied during 20 min of ischemia, with body temperature kept constant. Thus, the histopathological outcome of the brain damage, as assessed after 7 days of recovery, was strongly temperature dependent. Whereas ischemia at 37–38°C consistently caused neuronal necrosis in the hippocampus, neocortex, and caudoputamen, spontaneous cooling of the brain during ischemia at a rectal temperature of 37°C significantly reduced the ischemic damage. Intentional lowering of temperature to 35°C markedly reduced and to 33°C virtually prevented neuronal necrosis in some but not all of the regions studied. While damage to the caudoputamen was extremely temperature sensitive, that affecting the CA1 sector of the hippocampus, and particularly the lateral reticular nucleus of the thalamus, was less so. Our results suggest that whatever biochemical events are responsible for selective neuronal vulnerability, they are temperature sensitive; however, since there are differences in sensitivity between different parts of the brain, more than one mechanism may be involved.

scholarly journals Glucagon-Like Peptide-1 Decreases Intracerebral Glucose Content by Activating Hexokinase and Changing Glucose Clearance during Hyperglycemia

2012 ◽  
Vol 32 (12) ◽  
pp. 2146-2152 ◽  
Author(s):  
Michael Gejl ◽  
Lærke Egefjord ◽  
Susanne Lerche ◽  
Kim Vang ◽  
Bo Martin Bibby ◽  
...  
Keyword(s):  
Glucose Content ◽  
Brain Glucose ◽  
Glucose Levels ◽  
Hyperglycemic Clamp ◽  
Positron Emission ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Double Blinded ◽  
The Brain

Type 2 diabetes and hyperglycemia with the resulting increase of glucose concentrations in the brain impair the outcome of ischemic stroke, and may increase the risk of developing Alzheimer's disease (AD). Reports indicate that glucagon-like peptide-1 (GLP-1) may be neuroprotective in models of AD and stroke: Although the mechanism is unclear, glucose homeostasis appears to be important. We conducted a randomized, double-blinded, placebo-controlled crossover study in nine healthy males. Positron emission tomography was used to determine the effect of GLP-1 on cerebral glucose transport and metabolism during a hyperglycemic clamp with 18fluoro-deoxy-glucose as tracer. Glucagon-like peptide-1 lowered brain glucose ( P = 0.023) in all regions. The cerebral metabolic rate for glucose was increased everywhere ( P = 0.039) but not to the same extent in all regions ( P = 0.022). The unidirectional glucose transfer across the blood-brain barrier remained unchanged ( P = 0.099) in all regions, while the unidirectional clearance and the phosphorylation rate increased ( P = 0.013 and 0.017), leading to increased net clearance of the glucose tracer ( P = 0.006). We show that GLP-1 plays a role in a regulatory mechanism involved in the actions of GLUT1 and glucose metabolism: GLP-1 ensures less fluctuation of brain glucose levels in response to alterations in plasma glucose, which may prove to be neuroprotective during hyperglycemia.

scholarly journals Hippocampal Damage following Repeated Brief Hypotensive Episodes in the Rat

1991 ◽  
Vol 11 (6) ◽  
pp. 974-978 ◽  
Author(s):  
Yoichi Yamauchi ◽  
Hiroyuki Kato ◽  
Kyuya Kogure
Keyword(s):  
Brain Damage ◽  
Neuronal Damage ◽  
Neuronal Loss ◽  
Hippocampal Damage ◽  
Shed Blood ◽  
Arterial Blood ◽  
Hippocampal Ca1 ◽  
Severe Hypotension ◽  
The Brain ◽  
Hippocampal Ca1 Subfield

We examined the brain damage following repeated hypotensive episodes in the rat. Severe hypotension was induced by withdrawal of arterial blood. The MABP was maintained at about 25 mm Hg with isoelectric EEG and the shed blood was retransfused. After 1 week of recovery, histopathological changes were examined. No brain damage was observed after 1 min of isoelectric EEG. Mild neuronal damage to the hippocampal CA1 subfield was seen in some animals after two episodes of 1-min isoelectric EEG at a 1-h interval. Significant and consistent neuronal loss in the hippocampal CA1 subfield was observed after three episodes of 1-min isoelectric EEG. Scattered neuronal damage in the thalamus was additionally seen in some animals. The present study indicates that repeated brief hypotensive episodes produce brain damage depending on the number of episodes, even though no brain damage results when induced as a single insult. This animal model may reproduce hemodynamic transient ischemic attacks in humans.

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