Energy-requiring cell functions in the ischemic brain

1982 ◽  
Vol 56 (4) ◽  
pp. 482-497 ◽  
Author(s):  
Jens Astrup
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Global Cerebral Ischemia ◽  
Specific Inhibition ◽  
Ischemic Brain ◽  
Content Type ◽  
Cell Functions ◽  
The Brain ◽  
Fine Print

✓ The energy-requiring cell functions in the brain are described. The role of specific inhibition of these functions, and their critical low-supply levels of blood flow and oxygen are reviewed in relation to clinical management of focal and complete global cerebral ischemia.

Differences in critical cerebral blood flow with age in swine

1991 ◽  
Vol 75 (1) ◽  
pp. 103-107 ◽  
Author(s):  
Jun Harada ◽  
Akira Takaku ◽  
Shunro Endo ◽  
Naoya Kuwayama ◽  
Osamu Fukuda
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischemia ◽  
Content Type ◽  
Neonatal Pigs ◽  
S 100 ◽  
Newborn Pigs ◽  
Electroencephalogram Eeg ◽  
The Brain ◽  
Fine Print

✓ Normal cerebral blood flow (CBF), critical CBF at a flat reading of the electroencephalogram (EEG), and reversibility of the flat EEG after reperfusion were investigated in a total of 59 pigs, including seven newborns (1 to 3 days of age), 38 juveniles (1 month old), and 14 adults (7 months old). The CBF was determined by the hydrogen clearance method; the EEG was recorded continuously and a power spectrum analysis was performed. Cerebral ischemia was produced by occlusion of both common carotid arteries and induction of hypotension (approximately 50 mm Hg). The flat EEG reversibility was investigated for 3 hours after reperfusion. As parameters of brain development, the neuronal density and the time at which the S-100 protein appeared in the brain were examined. Normal CBF was highest in neonatal pigs and decreased with age. The critical CBF at a flat EEG was lowest in newborn pigs and was elevated with development of the brain. Tolerance against cerebral ischemia was greatest in newborn pigs.

Nonhyperemic blood flow restoration and brain edema in experimental focal cerebral ischemia

1989 ◽  
Vol 70 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Toshihiko Kuroiwa ◽  
Makoto Shibutani ◽  
Riki Okeda
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Brain Edema ◽  
Focal Cerebral Ischemia ◽  
Reactive Hyperemia ◽  
Diffusion Method ◽  
Left Middle Cerebral Artery ◽  
Content Type ◽  
Bbb Opening ◽  
Fine Print

✓ The effect of suppression of postischemic reactive hyperemia on the blood-brain barrier (BBB) and ischemic brain edema after temporary focal cerebral ischemia was studied in cats under ketamine and alpha-chloralose anesthesia. Regional cerebral blood flow (rCBF) was measured by a thermal diffusion method and a hydrogen clearance method. The animals were separated into three groups. In Group A, the left middle cerebral artery (MCA) was occluded for 6 hours. In Group B, the MCA was occluded for 3 hours and then reperfused for 3 hours; postischemic hyperemia was suppressed to the preischemic level by regulating the degree of MCA constriction. In Group C, the MCA was occluded for 3 hours and reperfused for 3 hours without suppressing the postischemic reactive hyperemia. The brain was removed and cut coronally at the site of rCBF measurement. The degree of ischemic edema was assessed by gravimetry in samples taken from the coronal section and correlated with the degree of BBB disruption at the corresponding sites, evaluated by densitometric determination of Evans blue discoloration. The findings showed that 1) ischemic edema was significantly exacerbated by postischemic hyperemia during reperfusion in parallel with the degree of BBB opening to serum proteins, and 2) suppression of postischemic hyperemia significantly reduced the exacerbation of ischemic edema and BBB opening. These findings indicate that blood flow may be restored without significant exacerbation of postischemic edema by the suppression of postischemic hyperemia in focal cerebral ischemia.

scholarly journals Accessing neuroinflammation sites: Monocyte/neutrophil-mediated drug delivery for cerebral ischemia

2019 ◽  
Vol 5 (7) ◽  
pp. eaau8301 ◽  
Author(s):  
Jia Hou ◽  
Xu Yang ◽  
Shiyi Li ◽  
Zhekang Cheng ◽  
Yuhua Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Flow ◽  
Cerebral Ischemia ◽  
Inflammatory Response ◽  
Target Cells ◽  
Ischemic Brain ◽  
Therapeutic Molecules ◽  
Cerebral Parenchyma ◽  
Cell Carriers ◽  
The Brain

Cerebral ischemia (CI) results from inadequate blood flow to the brain. The difficulty of delivering therapeutic molecules to lesions resulting from CI hinders the effective treatment of this disease. The inflammatory response following CI offers a unique opportunity for drug delivery to the ischemic brain and targeted cells because of the recruitment of leukocytes to the stroke core and penumbra. In the present study, neutrophils and monocytes were explored as cell carriers after selectively carrying cRGD liposomes, which effectively transmigrated the blood-brain barrier, infiltrated the cerebral parenchyma, and delivered therapeutic molecules to the injured sites and target cells. Our results showed the successful comigration of liposomes with neutrophils/monocytes and that both monocytes and neutrophils were important for successful delivery. Enhanced protection against ischemic injury was achieved in the CI/reperfusion model. The strategy presented here shows potential in the treatment of CI and other diseases related to inflammation.

Natural hypothermia immediately after transient global cerebral ischemia induced by spontaneous subarachnoid hemorrhage

2003 ◽  
Vol 98 (1) ◽  
pp. 50-56 ◽  
Author(s):  
Kiyoshi Takagi ◽  
Yoshiaki Tsuchiya ◽  
Kimiko Okinaga ◽  
Masafumi Hirata ◽  
Tadayoshi Nakagomi ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Body Temperature ◽  
Global Cerebral Ischemia ◽  
Control Group ◽  
Mean Body Temperature ◽  
Content Type ◽  
Transient Global Cerebral Ischemia ◽  
Gcs Score ◽  
Spontaneous Subarachnoid Hemorrhage ◽  
Fine Print

Object. Spontaneous subarachnoid hemorrhage (SAH) has an aspect of graded transient global cerebral ischemia. The purpose of the present study was the documentation of sequential changes in body temperature immediately after SAH-induced transient global cerebral ischemia in humans. Methods. Patients admitted within 12 hours after the initial onset of SAH were examined retrospectively (426 patients). Patients with unruptured cerebral aneurysms served as a control group (73 patients). Body temperature measured at the axilla on admission was analyzed. The grade of SAH was established according to the Glasgow Coma Scale (GCS): Grade I, GCS Score 15; Grade II, GCS Score 11 to 14; Grade III, GCS Score 8 to 10; Grade IV, GCS Score 4 to 7; and Grade V, GCS Score 3. The mean body temperature of patients in the control group was 36.49 ± 0.45°C (mean ± standard deviation). The mean body temperature of patients in the SAH group who had been admitted within 4 hours of onset for Grades I to V were significantly different (p < 0.001, analysis of variance [ANOVA]): 36.26 ± 0.7°C, 59 patients; 35.98 ± 0.85°C, 73 patients; 35.52 ± 0.79°C, 25 patients; 35.9 ± 1.09°C, 108 patients; and 35.56 ± 1.14°C, 73 patients, respectively. These values were significantly lower than those in control volunteers, except for patients with Grade I SAH. The reduction in body temperature was unrelated to the location of the cerebral aneurysm and was not the product of circadian rhythm. The temperatures of patients in the SAH group who were admitted beyond 4 hours after onset for each grade were significantly different (p < 0.01, ANOVA): 36.8 ± 0.91°C, 36 patients; 36.74 ± 0.68°C, 31 patients; 36.73 ± 0.38°C, three patients; 37.41 ± 1.37°C, 17 patients; and 38.9°C, one patient, respectively. These values were significantly higher than those in patients admitted within 4 hours of SAH onset for all grades except Grade V, and significantly higher than control values in patients with Grades I and IV SAH. Conclusions. These results indicate that body temperature falls and then rises immediately after the SAH-induced transient global cerebral ischemia without cardiac arrest in humans. The reduction in temperature may be a natural cerebral protection mechanism that is activated shortly after ischemic insult.

Microregional blood flow changes in experimental cerebral ischemia

1971 ◽  
Vol 35 (2) ◽  
pp. 155-166 ◽  
Author(s):  
Y. Lucas Yamamoto ◽  
Kathryne M. Phillips ◽  
Charles P. Hodge ◽  
William Feindel
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Fluorescein Angiography ◽  
Focal Cerebral Ischemia ◽  
Gamma Activity ◽  
Collateral Flow ◽  
Silicon Detectors ◽  
Content Type ◽  
Perfusion Flow ◽  
The Brain

✓ A branch of the middle cerebral artery on the convexity of the dog brain was occluded to produce an area of focal cerebral ischemia which could then be defined by fluorescein angiography of the brain. Repeated fluorescein angiography and measurement of microregional cerebral blood flow by xenon133 injected into the carotid artery and monitored by miniature lithium-drifted silicon detectors for gamma activity demonstrated that the ischemic zone was reduced in size by better collateral flow when the animals were allowed to breathe 5% carbon dioxide and 95% oxygen. Conversely, hyperventilation reducing the pCO2 made the ischemic zone larger by reducing collateral flow. No evidence was found to indicate that hypercapnia preferentially deprived the ischemic zone of perfusion flow. Retrograde collateral flow in the surface arteries appeared effective in terms of microcirculatory perfusion.

Thresholds of focal cerebral ischemia in awake monkeys

1981 ◽  
Vol 54 (6) ◽  
pp. 773-782 ◽  
Author(s):  
Thomas H. Jones ◽  
Richard B. Morawetz ◽  
Robert M. Crowell ◽  
Frank W. Marcoux ◽  
Stuart J. FitzGibbon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Neurological Function ◽  
Local Flow ◽  
Content Type ◽  
Mca Occlusion ◽  
Fine Print

✓ An awake-primate model has been developed which permits reversible middle cerebral artery (MCA) occlusion during physiological monitoring. This method eliminates the ischemia-modifying effects of anesthesia, and permits correlation of neurological function with cerebral blood flow (CBF) and neuropathology. The model was used to assess the brain's tolerance to focal cerebral ischemia. The MCA was occluded for 15 or 30 minutes, 2 to 3 hours, or permanently. Serial monitoring evaluated neurological function, local CBF (hydrogen clearance), and other physiological parameters (blood pressure, blood gases, and intracranial pressure). After 2 weeks, neuropathological evaluation identified infarcts and their relation to blood flow recording sites. Middle cerebral artery occlusion usually caused substantial decreases in local CBF. Variable reduction in flow correlated directly with the variable severity of deficit. Release of occlusion at up to 3 hours led to clinical improvement. Pathological examination showed microscopic foci of infarction after 15 to 30 minutes of ischemia, moderate to large infarcts after 2 to 3 hours of ischemia, and in most cases large infarcts after permanent MCA occlusion. Local CBF appeared to define thresholds for paralysis and infarction. When local flow dropped below about 23 cc/100 gm/min, reversible paralysis occurred. When local flow fell below 10 to 12 cc/100 gm/min for 2 to 3 hours or below 17 to 18 cc/100 gm/min during permanent occlusion, irreversible local damage was observed. These studies imply that some cases of acute hemiplegia, with blood flow in the paralysis range, might be improved by surgical revascularization. Studies of local CBF might help identify suitable cases for emergency revascularization.

Loss of cerebral regulation during cardiac output variations in focal cerebral ischemia

1992 ◽  
Vol 77 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Bruce I. Tranmer ◽  
Ted S. Keller ◽  
Glenn W. Kindt ◽  
David Archer
Keyword(s):  
Cardiac Output ◽  
Cerebral Ischemia ◽  
Blood Volume ◽  
Volume Expansion ◽  
Focal Cerebral Ischemia ◽  
Brain Regions ◽  
Ischemic Brain ◽  
Content Type ◽  
Blood Volume Expansion ◽  
Fine Print

✓ Focal cerebral ischemia was induced in anesthetized macaque monkeys by unilateral middle cerebral artery occlusion. The effect of blood volume expansion by a colloid agent and subsequent exsanguination to baseline cardiac output (CO) on local cerebral blood flow (CBF) was measured by the hydrogen clearance technique in both ischemic and nonischemic brain regions. Cardiac output was increased to maximum levels (159% ± 92%, mean ± standard error of the mean) by blood volume expansion with the colloid agent hetastarch, and was then reduced a similar amount (166% ± 82%) by exsanguination during the ischemic period. Local CBF in ischemic brain regions varied directly with CO, with a correlation coefficient of 0.89 (% change CBF/% change CO), while CBF in nonischemic brain was not affected by upward or downward manipulations of CO. The difference in these responses between ischemic and nonischemic brain was highly significant (p < 0.001). The results of this study show a profound loss of regulatory control in ischemic brain in response to alterations in CO, thereby suggesting that blood volume variations may cause significant changes in the intensity of ischemia. It is proposed that CO monitoring and manipulation may be vital for optimum care of patients with acute cerebral ischemia.

Alterations in Na+-K+-ATPase activity and β-endorphin content in acute ischemic brain with and without naloxone treatment

1990 ◽  
Vol 72 (3) ◽  
pp. 458-462 ◽  
Author(s):  
Tomoo Furui ◽  
Issei Tanaka ◽  
Kinjiro Iwata
Keyword(s):  
Atpase Activity ◽  
Cellular Membrane ◽  
Acute Stage ◽  
Contralateral Hemisphere ◽  
Ischemic Brain ◽  
Content Type ◽  
Mca Occlusion ◽  
The Brain ◽  
Naloxone Treatment ◽  
Fine Print

✓ The Na+-K+-adenosine triphosphatase (Na+-K+-ATPase) activity and β-endorphin immunoreactivity were determined in rat brain at the acute stage of ischemia produced by unilateral occlusion of the middle cerebral artery (MCA). The effect of pretreatment with naloxone on these activities was also evaluated in the same model. After MCA occlusion, Na+-K+-ATPase activity was promptly reduced in the ischemic hemisphere and remained at a lower level than in the contralateral hemisphere during 90 minutes of ischemia. A single intraperitoneal 0.5-mg injection of naloxone prior to MCA occlusion attenuated the inactivation. On the other hand, β-endorphin immunoreactivity was significantly increased following ischemia. The increase was marked in the ischemic hemisphere and was also observed in the contralateral hemisphere; this increase was not affected by the administration of naloxone. These results indicate the possibility that naloxone contributes to protecting the brain from ischemia through stabilizing the cellular membrane. The possible mechanism by which naloxone attenuates the inactivation of Na+-K+-ATPase in the ischemic brain is discussed in view of alterations of the central β-endorphin system during ischemia.

Cardiovascular responses to global cerebral ischemia: role of excitatory amino acids in the ventrolateral medullary pressor area

1993 ◽  
Vol 78 (6) ◽  
pp. 922-928 ◽  
Author(s):  
Robert F. Heary ◽  
Allen H. Maniker ◽  
Abbott J. Krieger ◽  
Hreday N. Sapru
Keyword(s):  
Amino Acids ◽  
Cerebral Ischemia ◽  
Excitatory Amino Acids ◽  
Excitatory Amino Acid ◽  
Cardiovascular Responses ◽  
Global Cerebral Ischemia ◽  
Content Type ◽  
Acid Receptor ◽  
Male Wistar Rats

✓ The object of this study was to investigate the role of the ventrolateral medullary pressor area in mediating the cardiovascular responses to experimentally induced global cerebral ischemia, and to test if excitatory amino acids or acetylcholine are the transmitters released in this brain region during these responses. The cerebral ischemic response was elicited in pentobarbital-anesthetized, artificially ventilated male Wistar rats by bilateral ligation of vertebral arteries followed by temporary clamping of the common carotid arteries. The pressor area was identified by microinjections of L-glutamate. Inhibition of neurons in this area by microinjections of muscimol, a γ-aminobutyric acid receptor agonist, abolished the ischemic response, which demonstrated that this area is important in mediating these responses. Microinjections of a broad-spectrum excitatory amino acid receptor blocker (kynurenate), of specific antagonists for N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors (injected alone or in combination), and of atropine failed to block the ischemic responses. These results indicate that: 1) the ventrolateral medullary pressor area mediates pressor responses to cerebral ischemia, and 2) excitatory amino acids or acetylcholine in this area do not mediate the cardiovascular responses to cerebral ischemia.

Spinal cord stimulation reducing infarct volume in a model of focal cerebral ischemia in rats

2003 ◽  
Vol 99 (1) ◽  
pp. 131-137 ◽  
Author(s):  
Oren Sagher ◽  
Dah-Luen Huang ◽  
Richard F. Keep
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischemia ◽  
Spinal Cord Stimulation ◽  
Focal Cerebral Ischemia ◽  
Doppler Flowmetry ◽  
Content Type ◽  
Baseline Values ◽  
Fine Print

Object. The authors previously showed that spinal cord stimulation (SCS) increases cerebral blood flow in rats, indicating that this technique may be useful in the treatment of focal cerebral ischemia. In the present study, the neuroprotective potential of SCS in the setting of middle cerebral artery occlusion (MCAO) was investigated. Methods. The authors induced permanent, focal cerebral ischemia by using either suture-induced occlusion or direct division of the MCA in Sprague—Dawley rats. Electrical stimulation of the cervical spinal cord was performed during cerebral ischemia. Cerebral blood flow was assessed using both laser Doppler flowmetry (LDF) and quantitative radiotracer analysis. Stroke volumes were analyzed after 6 hours of ischemia. Spinal cord stimulation resulted in a 52.7 ± 13.3% increase in LDF values (nine animals). Following MCAO, LDF values decreased by 64.1 ± 3.6% from baseline values (10 animals). Spinal cord stimulation subsequently increased LDF values to 30.9 ± 13.5% below original baseline values. These findings were corroborated using radiotracer studies. Spinal cord stimulation in the setting of transcranial MCAO significantly reduced stroke volumes as well (from 203 ± 33 mm3 [control] to 32 ± 8 mm3 [MCAO plus SCS], seven animals in each group, p < 0.001). Similarly, after suture-induced MCAO, SCS reduced stroke volumes (from 307 ± 29 mm3 [control] to 78 ± 22 mm3 [MCAO plus SCS], 10 animals in each group, p < 0.001). Conclusions. A strategy of performing SCS for the prevention of critical ischemia is feasible and may have the potential for the treatment and prevention of stroke.

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