Degeneration of Cholinergic Rat Basal Forebrain Neurons After Experimental Subarachnoid Hemorrhage

Löhr, Mario; Tzouras, Georgios; Molcanyi, Marek; Ernestus, Ralf Ingo; Hampl, Jürgen A.; Fischer, J.; Sahin, Kurtuluş; Arendt, Thomas; Härtig, Wolfgang

doi:10.1227/01.neu.0000320422.54985.6d

Cited by 11 publications

(7 citation statements)

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“…The findings of early neuronal damage were independent of peak ICP and the amount of subarachnoid blood. Using the ICP-controlled shunt model, the results extend prior findings [ 13 - 18 ] and suggest that CPP depletion at the time of SAH potentially triggers processes that eventually result in EBI after SAH.…”

Section: Discussionsupporting

confidence: 83%

“…It has been demonstrated that subarachnoid blood can cause direct brain damage, late rCBF reduction, and neuronal and astrocytic apoptosis independent of initial ICP increase [ 14 - 18 ]. However, we could not establish any relationship between the amount of subarachnoid blood and the degree of early (24 h) neuronal cell damage, either in close proximity to the brain surface (basal cortex) or in deep brain regions (hippocampus).…”

Section: Discussionmentioning

confidence: 99%

“…However, in this experimental setting, the extent of SAH was macroscopically more pronounced (reflected in a nearly four times higher hemoglobin concentration in the subarachnoid space basal brain areas) in animals with larger increase in ICP. And since subarachnoid blood per se is well known to cause direct brain damage, late rCBF reduction, and neuronal and astrocytic apoptosis independent of initial ICP increase [ 14 - 18 ], it still remains a matter of debate whether ICP increase or the extent of subarachnoid blood represents one of the main causes for increased EBI after SAH.…”

Section: Introductionmentioning

confidence: 99%

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Early brain injury linearly correlates with reduction in cerebral perfusion pressure during the hyperacute phase of subarachnoid hemorrhage

Marbacher

Neuschmelting

Andereggen

et al. 2014

ICMx

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BackgroundIt is unclear how complex pathophysiological mechanisms that result in early brain injury (EBI) after subarachnoid hemorrhage (SAH) are triggered. We investigate how peak intracranial pressure (ICP), amount of subarachnoid blood, and hyperacute depletion of cerebral perfusion pressure (CPP) correlate to the onset of EBI following experimental SAH.MethodsAn entire spectrum of various degrees of SAH severities measured as peak ICP was generated and controlled using the blood shunt SAH model in rabbits. Standard cardiovascular monitoring, ICP, CPP, and bilateral regional cerebral blood flow (rCBF) were continuously measured. Cells with DNA damage and neurodegeneration were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB).ResultsrCBF was significantly correlated to reduction in CPP during the initial 15 min after SAH in a linear regression pattern (r2 = 0.68, p < 0.001). FJB- and TUNEL-labeled cells were linearly correlated to reduction in CPP during the first 3 min of hemorrhage in the hippocampal regions (FJB: r2 = 0.50, p < 0.01; TUNEL: r2 = 0.35, p < 0.05), as well as in the basal cortex (TUNEL: r2 = 0.58, p < 0.01). EBI occurred in animals with severe (relative CPP depletion >0.4) and moderate (relative CPP depletion >0.25 but <0.4) SAH. Neuronal cell death was equally detected in vulnerable and more resistant brain regions.ConclusionsThe degree of EBI in terms of neuronal cell degeneration in both the hippocampal regions and the basal cortex linearly correlates with reduced CPP during hyperacute SAH. Temporary CPP reduction, however, is not solely responsible for EBI but potentially triggers processes that eventually result in early brain damage.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-014-0030-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Early brain injury linearly correlates with reduction in cerebral perfusion pressure during the hyperacute phase of subarachnoid hemorrhage

Marbacher

Neuschmelting

Andereggen

et al. 2014

ICMx

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“…Despite the fact that there is no direct vascular damage in this model, the distribution of blood is similar to that often seen after clinical SAH (Prunell et al, 2002), which most commonly involves the anterior circulation. Loss of forebrain cholinergic neurons and markers of inflammation and cell death are found in at least some animals up to a week after the experimental hemorrhage (Prunell et al, 2005a, b; Lohr et al, 2008). Further, a subset of animals show neurological deficits (Prunell et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Brainstem control of cerebral blood flow and application to acute vasospasm following experimental subarachnoid hemorrhage

et al. 2009

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Symptomatic ischemia following aneurysmal subarachnoid hemorrhage is common but poorly understood and inadequately treated. Severe constriction of the major arteries at the base of the brain, termed vasospasm, traditionally has been thought to be a proximal event underlying these ischemias, although microvascular changes also have been described. The vast majority of studies aimed at understanding the pathogenesis of ischemic deficits and vasospasm have focused on the interaction of the "spasmogen" of the extravasated blood with the smooth muscle and endothelium of the arteries. This has led to a comparative neglect of the contribution of the central nervous system to the maintenance of cerebral perfusion. In the present study, we focused on the role of the rostral ventromedial medulla (RVM) in modulating cerebral perfusion at rest and following an experimental subarachnoid hemorrhage in the rat. Changes in cerebral blood flow (CBF) were measured using laser-Doppler flowmetry and three-dimensional optical microangiography. Focal application of a GABA A receptor agonist and antagonist were used to respectively inactivate and activate the RVM. We show here that the RVM modulates cerebral blood flow under resting conditions, and further, contributes to restoration of cerebral perfusion following a high-grade subarachnoid hemorrhage. Failure of this brainstem compensatory mechanism could be significant for acute perfusion deficits seen in patients following subarachnoid hemorrhage.Keywords cerebral blood flow; subarachnoid hemorrhage; brainstem; modulation Symptomatic ischemic deficits remain poorly understood and inadequately treated sequelae of aneurysmal subarachnoid hemorrhage (SAH), and are seen in 25-30% of patients. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 October 6. Published in final edited form as:Neuroscience. Approximately half of those suffer permanent disability or death (Lombard and Borel, 2007). Vasospasm of the major arteries is thought to be a major contributor to the development of cerebral infarcts in these patients, although it is not necessary nor sufficient for all cases of ischemia (Macdonald et al., 2007).The majority of studies on the sequelae of SAH have focused on arterial smooth muscle and endothelium. Abnormal contraction of smooth muscle, free radical release, endothelial factors, nitric oxide, endothelins, inflammatory mediators, neuronal cell death and structural changes in the arterial wall have all been implicated. However, the focus on t...

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“…Conditions predominantly associated with a loss of one specific cell population, such as amyotrophic lateral sclerosis, Parkinson’s disease, or subarachnoid hemorrhage, may be targeted using specifically pre-differentiated cell grafts. In the case of traumatic or ischemic brain injury, a whole tissue segment (including neurons, glia, and vascular cells) has to be replaced by cells, which are able to differentiate into all lost cell types; alternatively, a heterogeneous graft containing different cell populations can also be used (Schouten et al, 2004; Molcanyi et al, 2007; Riess et al, 2007; Lohr et al, 2008; Burns et al, 2009; Richardson et al, 2010; Benchoua and Onteniente, 2011). …”

Section: Introductionmentioning

confidence: 99%

Impurity of Stem Cell Graft by Murine Embryonic Fibroblasts â€“ Implications for Cell-Based Therapy of the Central Nervous System

Molcanyi

Mehrjardi

Schäfer

et al. 2014

Front. Cell. Neurosci.

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Stem cells have been demonstrated to possess a therapeutic potential in experimental models of various central nervous system disorders, including stroke. The types of implanted cells appear to play a crucial role. Previously, groups of the stem cell network NRW implemented a feeder-based cell line within the scope of their projects, examining the implantation of stem cells after ischemic stroke and traumatic brain injury. Retrospective evaluation indicated the presence of spindle-shaped cells in several grafts implanted in injured animals, which indicated potential contamination by co-cultured feeder cells (murine embryonic fibroblasts – MEFs). Because feeder-based cell lines have been previously exposed to a justified criticism with regard to contamination by animal glycans, we aimed to evaluate the effects of stem cell/MEF co-transplantation. MEFs accounted for 5.3 ± 2.8% of all cells in the primary FACS-evaluated co-culture. Depending on the culture conditions and subsequent purification procedure, the MEF-fraction ranged from 0.9 to 9.9% of the cell suspensions in vitro. MEF survival and related formation of extracellular substances in vivo were observed after implantation into the uninjured rat brain. Impurity of the stem cell graft by MEFs interferes with translational strategies, which represents a threat to the potential recipient and may affect the graft microenvironment. The implications of these findings are critically discussed.

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Degeneration of Cholinergic Rat Basal Forebrain Neurons After Experimental Subarachnoid Hemorrhage

Abstract: The present study provides evidence for a decrease of cholinergic BFB neurons after SAH. The direct effect of blood in the basal cisterns seemed to result in an enduring tissue hypoxia as a significant mechanism for cholinergic degeneration.

Cited by 11 publications

References 54 publications

Early brain injury linearly correlates with reduction in cerebral perfusion pressure during the hyperacute phase of subarachnoid hemorrhage

Early brain injury linearly correlates with reduction in cerebral perfusion pressure during the hyperacute phase of subarachnoid hemorrhage

Brainstem control of cerebral blood flow and application to acute vasospasm following experimental subarachnoid hemorrhage

Impurity of Stem Cell Graft by Murine Embryonic Fibroblasts â€“ Implications for Cell-Based Therapy of the Central Nervous System

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