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Impact of stroke co-morbidities on cortical collateral flow following ischaemic stroke.

ABSTRACT: Acute hyperglycaemia and chronic hypertension worsen stroke outcome but their impact on collateral perfusion, a determinant of penumbral life span, is poorly understood. Laser-speckle contrast imaging (LSCI) was used to determine the influence of these stroke comorbidities on cortical perfusion after permanent middle cerebral artery occlusion (pMCAO) in spontaneously hypertensive stroke prone rats (SHRSP) and normotensive Wistar rats. Four independent studies were conducted. In animals without pMCAO, cortical perfusion remained stable over 180 min. Following pMCAO, cortical perfusion was markedly reduced at 30 min then gradually increased, via cortical collaterals, over the subsequent 3.5 h. In the contralateral non-ischaemic hemisphere, perfusion did not change over time. Acute hyperglycaemia (in normotensive Wistar) and chronic hypertension (SHRSP) attenuated the restoration of cortical perfusion after pMCAO. Inhaled nitric oxide did not influence cortical perfusion in SHRSP following pMCAO. Thus, hyperglycaemia at the time of arterial occlusion or pre-existing hypertension impaired the dynamic recruitment of cortical collaterals after pMCAO. The impairment of collateral recruitment may contribute to the detrimental effects these comorbidities have on stroke outcome.

SUBMITTER: Biose IJ

PROVIDER: S-EPMC7181095 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Impact of stroke co-morbidities on cortical collateral flow following ischaemic stroke.

Biose Ifechukwude J IJ Dewar Deborah D Macrae I Mhairi IM McCabe Christopher C

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20190624 5

Acute hyperglycaemia and chronic hypertension worsen stroke outcome but their impact on collateral perfusion, a determinant of penumbral life span, is poorly understood. Laser-speckle contrast imaging (LSCI) was used to determine the influence of these stroke comorbidities on cortical perfusion after permanent middle cerebral artery occlusion (pMCAO) in spontaneously hypertensive stroke prone rats (SHRSP) and normotensive Wistar rats. Four independent studies were conducted. In animals without p ...[more]

PMID: 31234703

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Project description:The neocortex and thalamus provide a core substrate for perception, cognition, and action, and are interconnected through different direct and indirect pathways that maintain specific dynamics associated with functional states including wakefulness and sleep. It has been shown that a lack of excitation, or enhanced subcortical inhibition, can disrupt this system and drive thalamic nuclei into an attractor state of low-frequency bursting and further entrainment of thalamo-cortical circuits, also called thalamo-cortical dysrhythmia (TCD). The question remains however whether similar TCD-like phenomena can arise with a cortical origin. For instance, in stroke, a cortical lesion could disrupt thalamo-cortical interactions through an attenuation of the excitatory drive onto the thalamus, creating an imbalance between excitation and inhibition that can lead to a state of TCD. Here we tested this hypothesis by comparing the resting-state EEG recordings of acute ischaemic stroke patients (N = 21) with those of healthy, age-matched control-subjects (N = 17). We observed that these patients displayed the hallmarks of TCD: a characteristic downward shift of dominant α-peaks in the EEG power spectra, together with increased power over the lower frequencies (δ and θ-range). Contrary to general observations in TCD, the patients also displayed a broad reduction in β-band activity. In order to explain the genesis of this stroke-induced TCD, we developed a biologically constrained model of a general thalamo-cortical module, allowing us to identify the specific cellular and network mechanisms involved. Our model showed that a lesion in the cortical component leads to sustained cell membrane hyperpolarization in the corresponding thalamic relay neurons, that in turn leads to the de-inactivation of voltage-gated T-type Ca2+-channels, switching neurons from tonic spiking to a pathological bursting regime. This thalamic bursting synchronises activity on a population level through divergent intrathalamic circuits, and entrains thalamo-cortical pathways by means of propagating low-frequency oscillations beyond the restricted region of the lesion. Hence, pathological stroke-induced thalamo-cortical dynamics can be the source of diaschisis, and account for the dissociation between lesion location and non-specific symptoms of stroke such as neuropathic pain and hemispatial neglect.

Project description:AIMS:The landmark STICH trial found that surgical revascularization compared to medical therapy alone improved survival in patients with heart failure (HF) of ischaemic aetiology and an ejection fraction (EF) ≤ 35%. However, the interaction between the burden of medical co-morbidities and the benefit from surgical revascularization has not been previously described in patients with ischaemic cardiomyopathy. METHODS AND RESULTS:The STICH trial (ClinicalTrials.gov Identifier: NCT00023595) enrolled patients ≥ 18 years of age with coronary artery disease amenable to coronary artery bypass grafting (CABG) and an EF ≤ 35%. Eligible participants were randomly assigned 1:1 to receive medical therapy (MED) (n = 602) or MED/CABG (n = 610). A modified Charlson co-morbidity index (CCI) based on the availability of data and study definitions was calculated by summing the weighted points for all co-morbid conditions. Patients were divided into mild/moderate (CCI 1-4) and severe (CCI ≥ 5) co-morbidity. Cox proportional hazards models were used to evaluate the association between CCI and outcomes and the interaction between severity of co-morbidity and treatment effect. The study population included 349 patients (29%) with a mild/moderate CCI score and 863 patients (71%) with a severe CCI score. Patients with a severe CCI score had greater functional limitations based on 6-min walk test and impairments in health-related quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire. A total of 161 patients (Kaplan-Meier rate = 50%) with a mild/moderate CCI score and 579 patients (Kaplan-Meier rate = 69%) with a severe CCI score died over a median follow-up of 9.8 years. After adjusting for baseline confounders, patients with a severe CCI score were at higher risk for all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.19-1.74; P < 0.001). There was no interaction between CCI score and treatment effect on survival (P = 0.756). CONCLUSIONS:More than 70% of patients had a severe burden of medical co-morbidities at baseline, which was independently associated with increased risk of death. There was not a differential benefit of surgical revascularization with respect to survival based on severity of co-morbidity.

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Impact of stroke co-morbidities on cortical collateral flow following ischaemic stroke.

Publications

Impact of stroke co-morbidities on cortical collateral flow following ischaemic stroke.

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