The effect of MK-801 and of brain-derived polypeptides on the development of ischemic lesion induced by photothrombotic occlusion of the distal middle cerebral artery in rats

Koroleva, V. I.; Korolev, O.S.; Loseva, E. V.; Bureš, Jan

doi:10.1016/s0006-8993(97)01448-0

Cited by 21 publications

(11 citation statements)

References 41 publications

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“…The balance of positive and negative sequelae of SD depended on the model, number of waves, and extent of general hypoxia, and the fundamentally changing properties of the SD itself. Morphological verification which we reported in [27] showed that the volume of cortical damage around the ischemic focus increased almost two-fold on administration of MK-801 as compared with the control group (22 • 3 and 13 • 2 mm 2 respectively). In the intact brain with a good blood supply, SD provokes intense episodes of vasodilation [28,34,41] and increases the efficiency of brain oxygen uptake and the rate of metabolic processes in nervous tissue [14,15,25,32,34].…”

Section: Discussionsupporting

confidence: 70%

“…The neurotropic action of Cerebrolysine has now been studied in clinical conditions and by experimental physiologists [13,27,39,40]. This preparation is a mixture of free amino acids (85%) and peptides (15%).…”

Section: Discussionmentioning

confidence: 99%

“…At the beginning of each experiment, KC1 microinjections induced control waves of SD, which spread across the cortex and were recorded by all electrodes. This type of anesthesia is known to lead to increases in the threshold for SD generation and to inhibit its propagation across the cortex [19,21,27,35]. Visual observation of events proceeding in response to illumination of the exposed brain surface showed that during thrombus formation in the MCA, the proximal parts of the artery swelled severely and that blood plasma started to flow through the vessel walls.…”

Section: Changes In the Constant Potential In Local Ismentioning

confidence: 99%

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Changes in the constant potential in brain structures in rats during focal ischemia and systemic hypoxia

Buresh

Koroleva

Korolev

et al. 1999

Neurosci Behav Physiol

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The functional consequences of spreading depression (SD) during the evolution of ischemic damage was studied in two models: focal cortical ischemia induced by photothrombosis of the middle cerebral artery (MCA) and systemic hypoxia induced by 0.8% carbon monoxide (CO). These studies showed that cortical waves of SD, arising spontaneously during MCA thrombosis and after arterial occlusion delayed thrombus formation and promoted the establishment of a collateral blood supply in the perifocal zone of ischemic lesions. The underlying mechanism consisted of episodes of intense vasodilation at the decay phase of every wave of SD. Respiration of 0.8% CO increased the blood carboxyhemoglobin level to 50-60%. In lightly anesthetized rats (pentobarbital 20 mg/kg), cortical and subcortical spontaneous waves of SD were transformed into stable hypoxic depolarization, leading to death of 60% of the animals or severe lesions of the central nervous system, in 20% of animals. Increases in the level of anesthesia (50 mg/kg anesthetic) prevented the spontaneous appearance of SD during long-lasting exposure to CO. In these conditions, experimentally induced waves of SD demonstrated that the hippocampus has a high sensitivity to moderate levels of hypoxia. The duration of hypoxic depolarization of the hippocampus, provoking a single SD wave, reached 30-60 min. Selective neuron damage in field CA1 was seen 30 days after hypoxia. Additionally, the left hippocampus of rats frequently showed profound morphological lesions in the form of "granules." Cerebrolysine (2.5 ml/kg daily for 10 days) completely prevented the formation of these lesions.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Changes In the Constant Potential In Local Ismentioning

confidence: 99%

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Changes in the constant potential in brain structures in rats during focal ischemia and systemic hypoxia

Buresh

Koroleva

Korolev

et al. 1999

Neurosci Behav Physiol

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“…Surprisingly, SD initiation and propagation do not require the generation or conduction of action potentials or chemical synaptic transmission (Balestrino, 1995;Largo et al, 1997;Basarsky et al, 1998), so SD is difficult to block pharmacologically. NMDA receptor antagonists can block SD in vivo (Hernandez-Caceres et al, 1987;Marrannes et al, 1988;Lauritzen and Hansen, 1992;Nellgard and Wieloch, 1992;Koroleva et al, 1998) and in brain slices (Somjen, 2001;Footitt and Newberry, 1998;Anderson and Andrew, 2002). Therefore some glutamate release is required to support SD propagation, but such release is not required for SD initiation (Obrenovitch et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Spreading Depression Expands Traumatic Injury in Neocortical Brain Slices

Church

Andrew²

2005

Journal of Neurotrauma

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Traumatic brain injury (TBI) is particularly common in young people, generating healthcare costs that can span decades. The cellular processes activated in the first minutes following injury are poorly understood, and the 3-4 h following trauma are crucial for reducing subsequent injury. Spreading depression (SD) is a profound inactivation of neurons and glia lasting 1-2 min that arises focally and migrates outward across gray matter. In the hours following focal stroke, the metabolic stress of energy reduction and recurring SD-like events (peri-infarct depolarizations, PIDs) interact to promote neuronal injury. Similar recurring depolarizations might evolve immediately following TBI and exacerbate neuronal damage peripheral to the impact site. To test this possibility and examine if certain drugs might limit damage by inhibiting what we term traumatic spreading depression (tSD), we developed a technique whereby a small weight was dropped onto a live slice of rat neocortex while imaging changes in light transmittance (LT). Imaging revealed a propagating front of increased LT arising at the border of the impact site. Traumatic SD significantly expanded the region of ensuing damage. Both tSD and subsequent damage were blocked by the NMDA receptor antagonist MK-801 (100 microM) or the sigma-1 receptor (sigma1R) ligands dextromethorphan (30 microM) or BD-1063 (100 microM). Co-application of the sigma1R antagonist (+)3-PPP with DM reversed the block as did lowering temperature from 35 degrees C to 32 degrees C. This study provides evidence that an event similar to peri-infarct depolarization can arise from an injury site in neocortex within seconds following impact and act to expand the region of acute neuronal damage.

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“…Due to the potentially positive and negative effects of injury depolarizations on the one hand and on the other, it is also a controversial issue whether direct inhibition of injury depolarizations, for example, using N-methyl-D-aspartate receptor (NMDAR) antagonists (Hertle et al 2012; Lauritzen and Hansen 1992;Marrannes et al 1988;Sakowitz et al 2009), would have a net beneficial effect (Reinhart and Shuttleworth 2018). This discussion is further complicated by the fact that NMDAR antagonists increasingly lose efficacy against injury depolarizations where they are increasingly harmful (Hernandez-Caceres et al 1987;Koroleva et al 1998;Lauritzen and Hansen 1992;Madry et al 2010;Muller and Somjen 1998). Thus, only a bathing medium containing high concentrations of, e.g., DNQX/NBQX to block all AMPA/kainate receptors, the combination of MK-801 and APV to potently block NMDARs, and bicuculline methiodide to block GABA A receptors succeeded in preventing the signature of injury depolarization on the single neuron level in severely ischemic (Allen et al 2004;Madry et al 2010) or anoxic brain slices (Revah et al 2016).…”

Section: Inhibiting Neuronal Mass Injury As a Target Of Neuroprotectimentioning

confidence: 99%

Direct electrophysiological evidence that spreading depolarization-induced spreading depression is the pathophysiological correlate of the migraine aura and a review of the spreading depolarization continuum of acute neuronal mass injury

et al. 2019

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Spreading depolarization is observed as a large negative shift of the direct current potential, swelling of neuronal somas, and dendritic beading in the brain's gray matter and represents a state of a potentially reversible mass injury. Its hallmark is the abrupt, massive ion translocation between intraneuronal and extracellular compartment that causes water uptake (= cytotoxic edema) and massive glutamate release. Dependent on the tissue's energy status, spreading depolarization can co-occur with different depression or silencing patterns of spontaneous activity. In adequately supplied tissue, spreading depolarization induces spreading depression of activity. In severely ischemic tissue, nonspreading depression of activity precedes spreading depolarization. The depression pattern determines the neurological deficit which is either spreading such as in migraine aura or migraine stroke or nonspreading such as in transient ischemic attack or typical stroke. Although a clinical distinction between spreading and nonspreading focal neurological deficits is useful because they are associated with different probabilities of permanent damage, it is important to note that spreading depolarization, the neuronal injury potential, occurs in all of these conditions. Here, we first review the scientific basis of the continuum of spreading depolarizations. Second, we highlight the transition zone of the continuum from reversibility to irreversibility using clinical

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The effect of MK-801 and of brain-derived polypeptides on the development of ischemic lesion induced by photothrombotic occlusion of the distal middle cerebral artery in rats

Cited by 21 publications

References 41 publications

Changes in the constant potential in brain structures in rats during focal ischemia and systemic hypoxia

Changes in the constant potential in brain structures in rats during focal ischemia and systemic hypoxia

Spreading Depression Expands Traumatic Injury in Neocortical Brain Slices

Direct electrophysiological evidence that spreading depolarization-induced spreading depression is the pathophysiological correlate of the migraine aura and a review of the spreading depolarization continuum of acute neuronal mass injury

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