Ischemia in the dorsal hippocampus is associated with acute extracellular release of dopamine and norepinephrine
TL;DR: Data demonstrate that ischemia in the dorsal hippocampus is associated with a mared release of DA and NE, which may contribute to the selective vulnerability of the lateral hippocampus to neuronal damage during ischemIA.
Abstract: The cerebral dialysis technique was employed to monitor extracellular concentrations of dopamine (DA), norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the dorsal hippocampus of gerbils before and after cerebral ischemia induced by carotid artery occlusion. Extracellular concentrations of DA and NE in the dorsal hippocampus increased from baseline levels of <35 fmol/collection interval to 180 and 200 fmol/collection, respectively, within 36 minutes following carotid artery ligation (n=8 animals). Extracellular concentrations of the DA metabolites, DOPAC and HVA, did not change significantly following carotid artery ligation. These data demonstrate that ischemia in the dorsal hippocampus is associated with a mared release of DA and NE. This release may contribute to the selective vulnerability of the dorsal hippocampus to neuronal damage during ischemia.
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TL;DR: It is unlikely that any one of these theories is fully capable of explaining the etiology or phenomenologic manifestations of delirium but rather that two or more of these act together to lead to the biochemical derangement and, ultimately, to the complex cognitive and behavioral changes characteristic ofdelirium.
Abstract: Delirium is a neurobehavioral syndrome caused by dysregulation of neuronal activity secondary to systemic disturbances. Over time, a number of theories have been proposed in an attempt to explain the processes leading to the development of delirium. Each proposed theory has focused on a specific mechanism or pathologic process (e.g., dopamine excess or acetylcholine deficiency theories), observational and experiential evidence (e.g., sleep deprivation, aging), or empirical data (e.g., specific pharmacologic agents' association with postoperative delirium, intraoperative hypoxia). This article represents a review of published literature and summarizes the top seven proposed theories and their interrelation. This review includes the "neuroinflammatory," "neuronal aging," "oxidative stress," "neurotransmitter deficiency," "neuroendocrine," "diurnal dysregulation," and "network disconnectivity" hypotheses. Most of these theories are complementary, rather than competing, with many areas of intersection and reciprocal influence. The literature suggests that many factors or mechanisms included in these theories lead to a final common outcome associated with an alteration in neurotransmitter synthesis, function, and/or availability that mediates the complex behavioral and cognitive changes observed in delirium. In general, the most commonly described neurotransmitter changes associated with delirium include deficiencies in acetylcholine and/or melatonin availability; excess in dopamine, norepinephrine, and/or glutamate release; and variable alterations (e.g., either a decreased or increased activity, depending on delirium presentation and cause) in serotonin, histamine, and/or γ-aminobutyric acid. In the end, it is unlikely that any one of these theories is fully capable of explaining the etiology or phenomenologic manifestations of delirium but rather that two or more of these, if not all, act together to lead to the biochemical derangement and, ultimately, to the complex cognitive and behavioral changes characteristic of delirium.
462 citations
TL;DR: Although the signal transduction pathways and intracellular molecular events during cerebral ischemia and reperfusion are complex, potential therapeutic neuroprotective strategies hold promise for the future.
298 citations
TL;DR: A pathoetiology-based cohesive model to better grasp the basic mechanisms that mediate this syndrome will serve clinicians well in aspiring to find ways to correct these cascades, instituting rational treatment modalities, and developing effective preventive techniques.
257 citations
Cites background from "Ischemia in the dorsal hippocampus ..."
...As in the case of DA, acute NE (NA noradrenaline in Europe, NE norepinephrine in the United States) released secondary to hypoxia or ischemia leads to further neuronal injury and the development of worsening of delirium [412]....
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TL;DR: It is shown that also in progressive MS, inflammation is the driving force for brain injury and that the discrepancy between inflammation-driven tissue injury and response to immunomodulatory therapies can be explained by different pathomechanisms acting in RRMS and progressive MS.
Abstract: Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system, which starts in the majority of patients with a relapsing/remitting MS (RRMS) course , which after several years of disease duration converts into a progressive disease. Since anti-inflammatory therapies and immune modulation exert a beneficial effect at the relapsing/remitting stage of the disease, but not in the progressive stage, the question was raised whether inflammation drives tissue damage in progressive MS at all. We show here that also in progressive MS, inflammation is the driving force for brain injury and that the discrepancy between inflammation-driven tissue injury and response to immunomodulatory therapies can be explained by different pathomechanisms acting in RRMS and progressive MS.
170 citations
Cites background from "Ischemia in the dorsal hippocampus ..."
...For example, under ischemic conditions, norepinephrine is released in excess into the extracellular space [69–72]....
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TL;DR: Experiments using rigid body- or head protection in animals subjected to blast showed that head protection failed to prevent inflammation in the brain or reduce neurological deficits, whereas body protection was successful in alleviating the blast-induced functional and morphological impairments in thebrain.
Abstract: Due to complex injurious environment where multiple blast effects interact with the body, parallel blast-induced neurotrauma is a unique clinical entity induced by systemic, local, and cerebral responses. Activation of autonomous nervous system; sudden pressure-increase in vital organs such as lungs and liver; and activation of neuroendocrine-immune system are among the most important mechanisms that contribute significantly to molecular changes and cascading injury mechanisms in the brain. It has been hypothesized that vagally mediated cerebral effects play a vital role in the early response to blast: this assumption has been supported by experiments where bilateral vagotomy mitigated bradycardia, hypotension, and apnea, and also prevented excessive metabolic alterations in the brain of animals exposed to blast. Clinical experience suggests specific blast-body-nervous system interactions such as 1) direct interaction with the head either through direct passage of the blast wave through the skull or by causing acceleration and/or rotation of the head; and 2) via hydraulic interaction, when the blast overpressure compresses the abdomen and chest, and transfers its kinetic energy to the body’s fluid phase, initiating oscillating waves that traverse the body and reach the brain. Accumulating evidence suggests that inflammation plays important role in the pathogenesis of long-term neurological deficits due to blast. These include memory decline, motor function and balance impairments, and behavioral alterations, among others. Experiments using rigid body- or head protection in animals subjected to blast showed that head protection failed to prevent inflammation in the brain or reduce neurological deficits, whereas body protection was successful in alleviating the blast-induced functional and morphological impairments in the brain.
145 citations
Cites background from "Ischemia in the dorsal hippocampus ..."
...Among the most important neuro-endocrine changes, an increase in norepinephrine (NE) synthesis and metabolism have been reported in animal experiments inducing transient cerebral ischemia (Globus et al., 1989; Bhardwaj et al., 1990), focal cortical lesions (Pappius, 1991), and fluid-percussion TBI (McIntosh et al....
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...…in norepinephrine (NE) synthesis and metabolism have been reported in animal experiments inducing transient cerebral ischemia (Globus et al., 1989; Bhardwaj et al., 1990), focal cortical lesions (Pappius, 1991), and fluid-percussion TBI (McIntosh et al., 1994) during the first hours after the…...
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References
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TL;DR: The unique delay in onset of ischemic cell change and the protracte increase in its incidence between 24 and 72 hours could reflect either delayed‐appearance of isChemic change in previously killed neurons or a delayed insult that continued to jeopardize compromised but otherwise viable neurons during the postischemic period.
Abstract: This study examined the temporal profile of ischemic neuronal damage following transient bilateral forebrain ischemia in the rat model of four-vessel occlusion. Wistar rats were subjected to transient but severe forebrain ischemia by permanently occluding the vertebral arteries and 24 hours later temporarily occluding the common carotid arteries for 10, 20, or 30 minutes. Carotid artery blood flow was restored and the rats were killed by perfusion-fixation after 3, 6, 24, and 72 hours. Rats with postischemic convulsions were discarded. Ischemic neuronal damage was graded in accordance with conventional neuropathological criteria. Ten minutes of four-vessel occlusion produced scattered ischemic cell change in the cerebral hemispheres of most rats. The time to onset of visible neuronal damage varied among brain regions and in some regions progressively worsened with time. After 30 minutes of ischemia, small to medium-sized striatal neurons were damaged early while the initiation of visible damage to hippocampal neurons in the h1 zone was delayed for 3 to 6 hours. The number of damaged neurons in neocortex (layer 3, layers 5 and 6, or both) and hippocampus (h1, h3-5, paramedian zone) increased significantly (p less than 0.01) between 24 and 72 hours. The unique delay in onset of ischemic cell change and the protracted increase in its incidence between 24 and 72 hours could reflect either delayed appearance of ischemic change in previously killed neurons or a delayed insult that continued to jeopardize compromised but otherwise viable neurons during the postischemic period.
2,729 citations
TL;DR: In the ventral part of the midbrain, essentially separate groups of aminergic and non-aminergic neurons in both the reticular formation (VTA) and in the adjacent nuclei of the raphe project bilaterally to a variety of similar terminal fields in the telencephalon, diencephal on, and brainstem.
1,693 citations
"Ischemia in the dorsal hippocampus ..." refers background in this paper
..., 1982) and receives DA projections from the ventral tegmentum and area A9 of the substantia nigra (Scatton et al., 1980; Swanson, 1982), we felt it reasonable to test whether DA is also released into the extracellular space of this brain region during ischemia....
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Journal Article•
TL;DR: Preliminary studies of the pharmacologic consequences of blockade of norepinephrine synthesis indicate impairment of motor activity and mild sedation in cats and guinea pigs and a reduction of the tyramine and nore Pinephrine pressor responses in guinea pig and rats.
Abstract: Repeated administration of the tyrosine hydroxylase inhibitor, α-methyl-tyrosine to guinea pigs decreased catecholamine levels in brain stem, caudate nucleus, heart and spleen to undetectable levels. Serotonin was unaffected. That the catecholamine decrease was a consequence of inhibition of tyrosine hydroxylase was shown by the following: tissue concentrations of norepinephrine failed to rise following monoamine oxidase inhibition and decarboxylase inhibitors failed to block the α-methyl-tyrosine effect; the conversion of tyrosine-C14 to norepinephrine was inhibited whereas that from dopa-H3 was not; and there was a normal uptake of exogenous norepinephrine by heart and spleen in animals pretreated with α-methyl-tyrosine. Preliminary studies of the pharmacologic consequences of blockade of norepinephrine synthesis indicate impairment of motor activity and mild sedation in cats and guinea pigs and a reduction of the tyramine and norepinephrine pressor responses in guinea pigs and rats.
833 citations
TL;DR: Dopaminergic afferents to the rat hippocampal formation originate from the A10 and A9 dopaminergic cell groups, and the 'anterior' hippocampusal formation receives a major input fromThe A10 area whereas the 'posterior' hippocampal region receives dopamine and DOPAC contents from both A9 and A10 cell groups.
332 citations
"Ischemia in the dorsal hippocampus ..." refers background in this paper
..., 1982) and receives DA projections from the ventral tegmentum and area A9 of the substantia nigra (Scatton et al., 1980; Swanson, 1982), we felt it reasonable to test whether DA is also released into the extracellular space of this brain region during ischemia....
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...The dorsal hippocampus, which like the striatum is also highly vulnerable to ischemia, also contains DA nerve terminals (Scatton et al., 1980; Ishikawa et al., 1982) which might release significant DA during ischemia....
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TL;DR: This study is the first to demonstrate that the presence of DA is a prerequisite for the development of ischemic injury in the striatum and that DA depletion protects thestriatum from isChemic damage.
277 citations
"Ischemia in the dorsal hippocampus ..." refers background in this paper
...protects intrinsic striatal neurons from damage during global ischemia in rats (Globus et al., 1987)....
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