Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review.

Background: Delayed cerebral ischemia represents a significant contributor to death and disability following aneurysmal subarachnoid hemorrhage. Although preclinical models have shown promising results, clinical trials have consistently failed to replicate the success of therapeutic strategies. The lack of standardized experimental setups and outcome assessments, particularly regarding secondary vasospastic/ischemic events, may be partly responsible for the translational failure.

Effect of isolated intracranial hypertension on cerebral perfusion within the phase of primary disturbances after subarachnoid hemorrhage in rats.

Introduction: Elevated intracranial pressure (ICP) and blood components are the main trigger factors starting the complex pathophysiological cascade following subarachnoid hemorrhage (SAH). It is not clear whether they independently contribute to tissue damage or whether their impact cannot be differentiated from each other. We here aimed to establish a rat intracranial hypertension model that allows distinguishing the effects of these two factors and investigating the relationship between elevated ICP and hypoperfusion very early after SAH.

Opening a window to the acutely injured brain: Simultaneous retinal and cerebral vascular monitoring in rats.

Many recent research projects have described typical chronic changes in the retinal vasculature for diverse neurovascular and neurodegenerative disorders such as stroke or Alzheimer's disease. Unlike cerebral vasculature, retinal blood vessels can be assessed non-invasively by retinal vessel analysis. To date, there is only a little information about potential simultaneous reactions of retinal and cerebral vessels in acute neurovascular diseases.

Procedural and Methodological Quality in Preclinical Stroke Research-A Cohort Analysis of the Rat MCAO Model Comparing Periods Before and After the Publication of STAIR/ARRIVE.

The translation of preclinical stroke research into successful human clinical trials remains a challenging task. The first Stroke Therapy Academic Industry Roundtable (STAIR) recommendations for preclinical research and several other guidelines were published to address these challenges. Most guidelines recommend the use of physiological monitoring to detect the occurrence of undesired pathologies such as subarachnoid hemorrhage and to limit the variability of the infarct volume and-therefore-homogenize the experimental result for complete reporting particularly with respect to transparency and methodological rigor.

Severity Assessment in Rats Undergoing Subarachnoid Hemorrhage Induction by Endovascular Perforation or Corresponding Sham Surgery.

Introduction: Animal models for preclinical research of subarachnoid hemorrhage (SAH) are widely used as much of the pathophysiology remains unknown. However, the burden of these models inflicted on the animals is not well characterized. The European directive requires severity assessment-based allocation to categories.

Neuroprotective Effects of the Inert Gas Argon on Experimental Traumatic Brain Injury In Vivo with the Controlled Cortical Impact Model in Mice.

Argon has shown neuroprotective effects after traumatic brain injury (TBI) and cerebral ischemia in vitro and in focal cerebral ischemia in vivo. The purpose of this study is to show whether argon beneficially impacts brain contusion volume (BCV) as the primary outcome parameter, as well as secondary outcome parameters, such as brain edema, intracranial pressure (ICP), neurological outcome, and cerebral blood flow (CBF) in an in-vivo model. Subjects were randomly assigned to either argon treatment or room air.

Burrowing behaviour of rats: Strain differences and applicability as well-being parameter after intracranial surgery.

In mice, burrowing is considered a species-typical parameter for assessing well-being, while this is less clear in rats. This exploratory study evaluated burrowing behaviour in three rat strains during training and in the direct postoperative phase after complex intracranial surgery in different neuroscience rat models established at Hannover Medical School or Aachen University Hospital. Male Crl:CD (SD;  = 18), BDIX/UlmHanZtm (BDIX;  = 8) and RjHan:WI (Wistar;  = 35) rats were individually trained to burrow gravel out of a tube on four consecutive days.

Vascular Reactivity to Hypercapnia Is Impaired in the Cerebral and Retinal Vasculature in the Acute Phase After Experimental Subarachnoid Hemorrhage.

Impaired cerebral blood flow (CBF) regulation, such as reduced reactivity to hypercapnia, contributes to the pathophysiology after aneurysmal subarachnoid hemorrhage (SAH), but temporal dynamics in the acute phase are unknown. Featuring comparable molecular regulation mechanisms, the retinal vessels participate in chronic and subacute stroke- and SAH-associated vessel alterations in patients and can be studied non-invasively. This study is aimed to characterize the temporal course of the cerebral and retinal vascular reactivity to hypercapnia in the acute phase after experimental SAH and compare the potential degree of impairment.

Retinal Vessel Responses to Flicker Stimulation Are Impaired in Ca 2.3-Deficient Mice-An Evaluation Using Retinal Vessel Analysis (RVA).

Metabolic demand increases with neuronal activity and adequate energy supply is ensured by neurovascular coupling (NVC). Impairments of NVC have been reported in the context of several diseases and may correlate with disease severity and outcome. Voltage-gated Ca-channels (VGCCs) are involved in the regulation of vasomotor tone.

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride.

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs-nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)-might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect.

Acute changes of pro-inflammatory markers and corticosterone in experimental subarachnoid haemorrhage: A prerequisite for severity assessment.

Many details of the pathophysiology of subarachnoid haemorrhage (SAH) still remain unknown, making animal experiments an indispensable tool for assessment of diagnostics and therapy. For animal protection and project authorization, one needs objective measures to evaluate the severity and burden in each model. Corticosterone is described as a sensitive stress parameter reflecting the acute burden, and inflammatory markers can be used for assessment of the extent of the brain lesion.

Perspective review of optical imaging in welfare assessment in animal-based research.

To refine animal research, vital signs, activity, stress, and pain must be monitored. In chronic studies, some measures can be assessed using telemetry sensors. Although this methodology provides high-precision data, an initial surgery for device implantation is necessary, potentially leading to stress, wound infections, and restriction of motion.

Assessment of cerebral hemodynamics during neurosurgical procedures using laser speckle image analysis.

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe medical condition associated with a significant cause of mortality throughout the world. Cisterna magna injection model is accepted widely to mimic clinical aSAH and is performed on small animal models to study aSAH during neurosurgery. Coherent light scattered from the surface of the rat brain is used to infer information about the variations in blood flow during this condition.

The Acute Phase of Experimental Subarachnoid Hemorrhage: Intracranial Pressure Dynamics and Their Effect on Cerebral Blood Flow and Autoregulation.

Clinical presentation and neurological outcome in subarachnoid hemorrhage (SAH) is highly variable. Aneurysmal SAH (aSAH) is hallmarked by sudden increase of intracranial pressure (ICP) and acute hypoperfusion contributing to early brain injury (EBI) and worse outcome, while milder or non-aneurysmal SAH with comparable amount of blood are associated with better neurological outcome, possibly due to less dramatic changes in ICP. Acute pressure dynamics may therefore be an important pathophysiological aspect determining neurological complications and outcome.

Non-invasive evaluation of neurovascular coupling in the murine retina by dynamic retinal vessel analysis.

Background: Impairment of neurovascular coupling (NVC) was recently reported in the context of subarachnoid hemorrhage and may correlate with disease severity and outcome. However, previous techniques to evaluate NVC required invasive procedures. Retinal vessels may represent an alternative option for non-invasive assessment of NVC.

Pilot study to assess visualization and therapy of inflammatory mechanisms after vessel reopening in a mouse stroke model.

After reperfusion therapy in stroke patients secondary inflammatory processes may increase cerebral damage. In this pilot study, effects of anti-inflammatory therapy were assessed in a middle cerebral artery occlusion (MCAO) mouse model after reperfusion. 1 hour after MCAO, the artery was reopened and tacrolimus or NaCl were administered intra-arterially.

Unconjugated bilirubin modulates neuronal signaling only in wild-type mice, but not after ablation of the R-type/Ca 2.3 voltage-gated calcium channel.

Introduction: The relationship between blood metabolites and hemoglobin degradation products (BMHDPs) formed in the cerebrospinal fluid and the development of vasospasm and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) has been the focus of several previous studies, but their molecular and cellular targets remain to be elucidated.

Methods: Because BMHDP-induced changes in Ca 2.3 channel function are thought to contribute to DCI after aSAH, we studied their modulation by unconjugated bilirubin (UCB) in an organotypical neuronal network from wild-type (WT) and Ca 2.

Severity assessment and scoring for neurosurgical models in rodents.

The most important acute neurological diseases seen at neurosurgery departments are traumatic brain injuries (TBI) and subarachnoid hemorrhages (SAH). In both diseases the pathophysiological sequela are complex and have not been fully understood up to now, and rodent models using rats and mice are most suitable for the investigation of the pathophysiological details. In both models, surgery is performed under anesthesia, followed by assessment of their functional outcome and behavioral testing before brain tissue analysis after euthanasia.

A role of the sodium pump in spreading ischemia in rats.

In rats, spreading depolarization induces vasodilation/hyperemia in naïve tissue but the inverse response when artificial cerebrospinal fluid is topically applied to the brain containing (a) a nitric oxide-lowering agent and (b) elevated K. The inverse response is characterized by severe vasoconstriction/ischemia. The perfusion deficit runs together with the depolarization in the tissue (=spreading ischemia).

Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common inherited small-vessel disease, is associated with vascular aggregation of mutant Notch3 protein, dysfunction of cerebral vessels, and dementia. Pericytes, perivascular cells involved in microvascular function, express Notch3. Therefore, we hypothesize that these cells may play a role in the pathogenesis of CADASIL.

Silver nanoparticle dissolution in the presence of ligands and of hydrogen peroxide.

Dissolution of silver nanoparticles (AgNP with carbonate or citrate coating, total Ag 1-5 μM) was examined in the presence of the ligands cysteine, chloride and fulvic acids and of the oxidant hydrogen peroxide (H2O2) at low concentrations at pH 7.5. Dissolved Ag was separated from AgNP by ultrafiltration.

Functional real-time optoacoustic imaging of middle cerebral artery occlusion in mice.

Background And Purpose: Longitudinal functional imaging studies of stroke are key in identifying the disease progression and possible therapeutic interventions. Here we investigate the applicability of real-time functional optoacoustic imaging for monitoring of stroke progression in the whole brain of living animals.

Materials And Methods: The middle cerebral artery occlusion (MCAO) was used to model stroke in mice, which were imaged preoperatively and the occlusion was kept in place for 60 minutes, after which optoacoustic scans were taken at several time points.

Sugar for the brain: the role of glucose in physiological and pathological brain function.

The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology.

Simultaneous imaging of cortical blood flow and haemoglobin concentration with LASCA and RGB reflectometry.

We demonstrate a system for the simultaneous imaging of cortical blood flow and haemoglobin oxygenation by laser speckle contrast analysis (LASCA) and RGB reflectometry. The sensitivity of the system was tested by observing changes of haemoglobin oxygenation and blood flow in rats in response to ischaemic stroke, hypercapnia, hyperoxia, hypoxia, cortical spreading depression and cortical activation following forepaw stimulation.

Essential role of interleukin-6 in post-stroke angiogenesis.

Ambivalent effects of interleukin-6 on the pathogenesis of ischaemic stroke have been reported. However, to date, the long-term actions of interleukin-6 after stroke have not been investigated. Here, we subjected interleukin-6 knockout (IL-6(-/-)) and wild-type control mice to mild brain ischaemia by 30-min filamentous middle cerebral artery occlusion/reperfusion.