scholarly journals Acidosis Induced by Hypercapnia Exaggerates Ischemic Brain Damage

1994 ◽  
Vol 14 (2) ◽  
pp. 243-250 ◽  
Author(s):  
Ken-Ichiro Katsura ◽  
Tibor Kristián ◽  
Maj-Lis Smith ◽  
Bo K. Siesjö
Keyword(s):  
Brain Damage ◽  
Extracellular Ph ◽  
Ischemic Damage ◽  
Forebrain Ischemia ◽  
Transient Ischemia ◽  
Short Term ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Tissue Acidosis ◽  
The Brain

Although preischemic hyperglycemia is known to aggravate damage due to transient ischemia, it is a matter of controversy whether or not this is a result of the exaggerated acidosis. It has recently been reported that although tissue acidosis of a comparable severity could be induced in normoglycemic dogs by an excessive rise in arterial CO2 tension, short-term functional recovery was improved, rather than compromised. In the present experiments we induced excessive hypercapnia (Paco2, ∼300 mm Hg) in normoglycemic rats before inducing forebrain ischemia of 10-min duration. This reduced the brain extracellular pH to values normally encountered in hyperglycemic rats subjected to ischemia. The events induced by hypercapnia clearly enhanced ischemic brain damage, as assessed histologically after 7 days of recovery. We hypothesize that the decisive event was an exaggerated decrease in extra- and intracellular pH and that the results thus demonstrate an adverse effect of acidosis. However, since postischemic seizures did not occur in the hypercapnic ischemic rats, the results also demonstrate that changes in intra-extracellular pH and bicarbonate concentrations modulated ischemic damage in an unexpected way.

scholarly journals Characteristics of nervous tissue after modeling of focal cerebral ischemia in rats at different periods of reperfusion

2018 ◽  
Vol 24 (3) ◽  
pp. 58-64
Author(s):  
O.I. Savchuk ◽  
G.G. Skibo
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Nervous Tissue ◽  
Focal Cerebral Ischemia ◽  
Tactile Sensitivity ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Ischemic Period ◽  
The Brain ◽  
Occlusion Period

The stroke-causing problems are extremely important in Ukraine. This makes a heavy burden not only on the health care system, but also on the whole society as a whole. That's why we've studied structural and ultrastructural changes of cortical neurons and striatum of the brain and the development of delayed death of nerve cells after the modeling of the middle cerebral artery occlusion (MCAO) and post ischemic period in rats. We've analyzed the data at different terms after modeling of MCAO. The purpose of the study was to investigate the changes in the nervous tissue in the modeling of focal cerebral ischemia by monofilament occlusion of MCAO in rats at different periods of reperfusion. The statistical processing of primary digital experimental data was carried out using the software Statistica 6.0. It was confirmed that the 60-minute occlusion of the MCAO is an adequate model of focal ischemic brain damage in rats. Changes of locomotor activity and a tactile sensitivity were determined in rats after occlusion and after reperfusion during the post-period period. It was found that in the experimental group with a reperfusion period of 72 hours, a clear increase of the volume of the ischemic area of the brain, accompanied by significant neurological deficiency, was observed. Reduced research activity of the rats was revealed, which was shown in the decrease of the number of squares they crossed, the number of racks, the increase of acts of grooming and the duration of acts of frizings. Following ischemic brain damage, there was also a disbalance of somato-sensory functions, as evidenced by an increase in the time during which the animal took a test stimulus ("Sticky tape") from both the anterior paws when tested for tactile sensitivity (adhesive removal test). An electron microscopic study of the cortex showed that dark wrinkled neurons and enlightened swollen neurons were observed at 72 hours of post-occlusion period, indicating different ways of death of these cells. Changes in striatum were similar to changes in the cortex, which progressed with an increase in the post-occlusion period. The protocol of the serial evaluation of neurological disorders used after MCAO modeling allowed detecting long-term stable functional disorders in laboratory rats. The obtained data indicate significant changes in the structure of the cortex and striatum in the post-ischemic period and the progressive nature of these changes.

Significant Role of microRNA-182-5p in Neonatal Hypoxic-Ischemic Injury and Related Mechanism

2020 ◽  
Vol 10 (5) ◽  
pp. 654-661
Author(s):  
Qin Wang ◽  
Ting Wang
Keyword(s):  
Cell Viability ◽  
Brain Tissue ◽  
Brain Damage ◽  
Rat Model ◽  
Target Gene ◽  
Luciferase Reporter ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Qrt Pcr ◽  
The Brain

The purpose of current study was to explore the role and mechanism of microRNA-182-5p (miR182-5p) in neonatal hypoxic ischemic brain damage (HIBD). First, we established a hypoxic-ischemic (HI) rat model and assessed the neurological function of the rats using the Zea Longa score. Then, the level of miR-182-5p in brain tissue of neonatal rats was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Findings revealed that miR-182-5p was significantly down-regulated in the brain tissue of HI rat model. Next, we studied the target gene of miR-182-5p by using TargetScan and dual luciferase reporter assay. Results showed that CASP2 was a direct target gene of miR-182-5p, and the level of CASP2 was significantly up-regulated in the brain tissue of HI rat model. Immediately thereafter, we established an oxygen and glucose deprivation (OGD) cell model of primary cortical neurons, and demonstrated the changes of miR182-5p in cells treated with OGD by qRT-PCR. Finally, to determine the function of miR-182-5p in OGD subjected neuronal cells, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry (FCM) assays were used to study cell viability and apoptosis. The study found that compared with the OGD group, miR-182-5p mimic significantly increased nerve cell viability, reduced cell apoptosis and decreased cleaved-Caspase3/7/8 protein expression, however, all these changes were significantly reversed by overexpression of the CASP2 gene. Taken together, miR-182-5p might protect the nerve cells from ischemia and hypoxia by targeting CASP2, thereby playing a protective role in hypoxic ischemic encephalopathy, which might be a new effective target for neonatal hypoxic ischemic brain damage treatment.

scholarly journals Protective Effect of the Glutamate Antagonist, MK-801 in Focal Cerebral Ischemia in the Cat

1988 ◽  
Vol 8 (1) ◽  
pp. 138-143 ◽  
Author(s):  
E. Ozyurt ◽  
D. I. Graham ◽  
G. N. Woodruff ◽  
J. McCulloch
Keyword(s):  
Cerebral Ischemia ◽  
Nmda Receptor ◽  
Middle Cerebral Artery ◽  
Brain Damage ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Ischemic Damage ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Mk 801

The effects of the glutamate N-methyl-D aspartate (NMDA) receptor antagonist, MK-801, upon ischemic brain damage has been examined in anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of one middle cerebral artery and the animals were killed 6 h later. The amount of early ischemic damage was assessed in coronal sections at 16 predetermined stereotactic planes. Pretreatment with MK-801 (5 mg/kg, i.v.), 30 min before occlusion of the middle cerebral artery significantly reduced the volume of ischemic damage (from 32.7 ± 4.0% of the cerebral hemisphere in vehicle-treated cats to 16.2 ± 4.5% in MK-801-treated cats). NMDA receptor antagonists that penetrate the blood-brain barrier, such as MK-801, merit further study as protective agents against ischemic brain damage.

scholarly journals Hydrogen inhalation protects hypoxic–ischemic brain damage by attenuating inflammation and apoptosis in neonatal rats

2019 ◽  
Vol 244 (12) ◽  
pp. 1017-1027 ◽  
Author(s):  
Guojiao Wu ◽  
Zhiheng Chen ◽  
Peipei Wang ◽  
Mingyi Zhao ◽  
Masayuki Fujino ◽  
...  
Keyword(s):  
Brain Injury ◽  
Inflammatory Response ◽  
Spatial Memory ◽  
Brain Damage ◽  
Morris Water Maze Test ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Hypoxia Ischemia ◽  
The Brain

Hypoxic–ischemic brain damage (HIBD) is one of the leading causes of brain injury in infant with high risk of mortality and disability; therefore, it is important to explore more feasible and effective treatment strategies. Here, we assessed the neuroprotective effects of different hydrogen inhalation times for the treatment of HIBD. We induced hypoxia–ischemia in Sprague–Dawley rats (postnatal day 7, both sexes), followed by treatment with hydrogen inhalation for 30, 60, or 90 min. Morphological brain injury was assessed by Nissl and TUNEL staining. Acute inflammation was evaluated by examining the expression of interleukin-1β (IL-1β) and NF-κB p65, as well as Iba-1 immunofluorescence in the brain. Neural apoptosis was evaluated by examining the expression of P-JNK and p53 as well as NeuN immunofluorescence. Neurobehavioral function of rats was evaluated by Morris water maze test at 36 days after surgery. The results showed that hypoxia–ischemia injury induced the inflammatory response of microglia; however, these changes were inhibited by hydrogen inhalation. The inhibitory effects became more apparent as the treatment duration increased ( P < 0.05). Furthermore, hypoxia–ischemia induced neuronal damage and increased the expression of the apoptotic factors, P-JNK, and p53, which were attenuated by hydrogen inhalation ( P < 0.05). Hypoxia–ischemia caused long-term spatial memory deficits during brain maturation, which were ameliorated by hydrogen inhalation ( P < 0.01). In conclusion, hypoxia–ischemia induced severe long-term damage to the brain, which could be alleviated by hydrogen inhalation in a time-dependent manner. Impact statement Oxidative stress is known to be involved in the main pathological progression of neonatal hypoxic–ischemic brain damage (HIBD). Hydrogen (H2) is an antioxidant that can be used to treat HIBD; however, the mechanism by which hydrogen may be used as a promising treatment for neonates with HIBD is not very clear. This study demonstrated that inhaled H2 is neuroprotective against HIBD in SpragueDawley rats by inhibiting the brain’s inflammatory response and neuronal apoptosis or damage and protecting against spatial memory decline. Further, this study showed that inhaled H2 has potential as a therapeutic approach for HIBD. This is relevant to clinical treatment protocols when hypoxia–ischemia is suspected in neonates.

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.

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