Viability thresholds and the penumbra of focal ischemia

Annals of Neurology, Год журнала: 1994, Номер 36(4), С. 557 - 565

Опубликована: Окт. 1, 1994

Abstract The classic concept of the viability thresholds ischemia differentiates between two critical flow rates, threshold electrical failure and membrane failure. These mark upper lower limits ischemic penumbra which is thought ot suffer only functional but not structural injury. Recent studies metabolic disturbances suggest a more complex pattern thresholds. At declining protein synthesis inhibited at first (at about 0.55 ml/gm/min), followed by stimulation anaerobic glycolysis 0.35 release neurotransmitters beginning disturbance energy metabolism 0.20 ml/min), finally anoxic depolariztion (<0.15 ml/gm/min). penumbra, as defined thresholds, does remain viable for extended periods. Since tissue requires maintenance energy‐dependent processes, redefined region constrained blood supply in preserved. Imaging combining autoradiographic cerebral measurements with bioluminescent images adenosine triphosphate (ATP) demonstrates gradual expansion infarct core (in ATP depleted) into until, after few hours, has disappeared. It suggested that limited survival due to periinfarct depolarizations, result repeated episodes hypoxia, because increased workload coupled an adequate increase collateral supply. This explains pharmacological suppression depolarizations lowering reducing volume infarct.

Язык: Английский

---

Cyclo-Oxygenase-2 Gene Expression in Neurons Contributes to Ischemic Brain Damage

Journal of Neuroscience, Год журнала: 1997, Номер 17(8), С. 2746 - 2755

Опубликована: Апрель 15, 1997

Cyclo-oxygenase-2 (COX-2), a rate-limiting enzyme for prostanoid synthesis, is induced during inflammation and participates in inflammation-mediated cytotoxicity. Cerebral ischemia followed by an inflammatory reaction that plays role the evolution of tissue damage. We studied whether COX-2 after cerebral if so, such expression contributes to ischemic brain The middle artery was occluded rats, area sampled analysis 3–96 hr later. mRNA determined competitive reverse-transcription PCR. upregulated hemisphere, but not contralaterally, beginning 6 ischemia. upregulation reached maximum at 12 hr, which time fivefold induction message occurred. Twenty-four hours ischemia, concentration prostaglandin E 2 elevated injured 292 ± 57% ( n = 6). immunoreactivity observed neurons medial edge area. Administration inhibitor NS-398 attenuated elevation postischemic reduced volume infarct 29 6% p < 0.05). Thus, leads message, protein, products hemisphere. data implicate mechanisms delayed neuronal death border provide rationale neuroprotective strategies employing inhibitors.

Язык: Английский

---

Specific Role of Tight Junction Proteins Claudin-5, Occludin, and ZO-1 of the Blood–Brain Barrier in a Focal Cerebral Ischemic Insult

Journal of Molecular Neuroscience, Год журнала: 2011, Номер 44(2), С. 130 - 139

Опубликована: Фев. 11, 2011

Язык: Английский

---

Role of microglia in stroke

Glia, Год журнала: 2024, Номер 72(6), С. 1016 - 1053

Опубликована: Янв. 4, 2024

Abstract Microglia play key roles in the post‐ischemic inflammatory response and damaged tissue removal reacting rapidly to disturbances caused by ischemia working restore lost homeostasis. However, modified environment, encompassing ionic imbalances, disruption of crucial neuron–microglia interactions, spreading depolarization, generation danger signals from necrotic neurons, induce morphological phenotypic shifts microglia. This leads them adopt a proinflammatory profile heighten their phagocytic activity. From day three post‐ischemia, macrophages infiltrate core while microglia amass at periphery. Further, inflammation prompts metabolic shift favoring glycolysis, pentose‐phosphate shunt, lipid synthesis. These shifts, combined with intake, drive droplet biogenesis, fuel anabolism, enable proliferation. Proliferating release trophic factors contributing protection repair. some accumulate lipids persistently transform into dysfunctional potentially harmful foam cells. Studies also showed that either display impaired apoptotic cell clearance, or eliminate synapses, viable endothelial Yet, it will be essential elucidate viability engulfed cells, features local extent damage, temporal sequence. Ischemia provides rich variety region‐ injury‐dependent stimuli for microglia, evolving time generating distinct phenotypes including those exhibiting traits others showing pro‐repair features. Accurate profiling phenotypes, alongside more precise understanding associated conditions, is necessary step serve as potential foundation focused interventions human stroke.

Язык: Английский

---

Progression of ischaemic stroke and excitotoxic aminoacids

The Lancet, Год журнала: 1997, Номер 349(9045), С. 79 - 82

Опубликована: Янв. 1, 1997

Язык: Английский

---

Spreading depression: a review of the clinical relevance

Brain Research Reviews, Год журнала: 2001, Номер 38(1-2), С. 33 - 60

Опубликована: Дек. 1, 2001

Язык: Английский

---

Altered glutamatergic transmission in neurological disorders: From high extracellular glutamate to excessive synaptic efficacy

Progress in Neurobiology, Год журнала: 1997, Номер 51(1), С. 39 - 87

Опубликована: Янв. 1, 1997

Язык: Английский

---

Cellular mechanisms underlying acquired epilepsy: The calcium hypothesis of the induction and maintainance of epilepsy

Pharmacology & Therapeutics, Год журнала: 2004, Номер 105(3), С. 229 - 266

Опубликована: Дек. 13, 2004

Язык: Английский

---

Cellular and Molecular Pathways of Ischemic Neuronal Death

BMB Reports, Год журнала: 2002, Номер 35(1), С. 67 - 86

Опубликована: Янв. 31, 2002

Three routes have been identified triggering neuronal death under physiological and pathological conditions. Excess activation of ionotropic glutamate receptors cause influx accumulation $Ca^{2+}$ $Na^+$ that result in rapid swelling subsequent within a few hours. The second route is caused by oxidative stress due to reactive oxygen nitrogen species. Apoptosis or programmed cell often occurs during developmental process has coined as additional the mature nervous system. Evidence being accumulated excitotoxicity, stress, apoptosis propagate through distinctive mutually exclusive signal transduction pathway contribute loss following hypoxic-ischemic brain injury. Thus, therapeutic intervention injury should be aimed prevent concerted way.

Язык: Английский

---

Neuroserpin reduces cerebral infarct volume and protects neurons from ischemia-induced apoptosis

Blood, Год журнала: 2000, Номер 96(2), С. 569 - 576

Опубликована: Июль 15, 2000

Язык: Английский

---