Prefrontal Cortex as a Central Hub of Structural Diaschisis Following Subcortical Stroke

 You created nothing here that gets survivors recovered! Here is how fucking long this has been out there; WITH NOTHING BEING DONE TO GET SURVIVORS RECOVERED!

The Role of Diaschisis in Stroke Recovery March 2018 

The latest useless crapola here: 

Prefrontal Cortex as a Central Hub of Structural Diaschisis Following Subcortical Stroke

Yuanyuan Li, MD https://orcid.org/0009-0002-9403-9805, Xinyue Shi, MD https://orcid.org/0009-0008-8174-5077, Yan Shen, MD, Linlu Wu, MB, Xirui Sun, MB, Kang Wu, MD, PhD, Kuangshi Li, MD, PhD https://orcid.org/0000-0001-7998-269X, … Show All … , and Yihuai Zou, MD, PhD https://orcid.org/0000-0002-4003-8244 zouyihuai2004@163.comAuthor Info & Affiliations

Stroke

New online

https://doi.org/10.1161/STROKEAHA.125.051768

Abstract

BACKGROUND:After a subcortical stroke, structural and functional alterations have often been observed in brain regions far from the lesion, a phenomenon suspected but not yet confirmed as diaschisis. This study investigated the existence and patterns of diaschisis following subcortical stroke.

METHODS:This observational, single-center, cross-sectional study was conducted in China from August 2014 to September 2023. We recruited patients with subcortical stroke with hemiplegia and unilateral lesions in the basal ganglia and corona radiata. Healthy controls were recruited from the community using an age- and sex-matching strategy with the patients. Patients were categorized by the National Institutes of Health Stroke Scale scores: mild (<5) and moderate (5–15) deficits. Using magnetic resonance imaging techniques, we analyzed gray matter volume alterations with voxel-based morphometry and causal structural networks with the causal structural covariance network method.

RESULTS:Of the 566 patients initially screened, 102 were enrolled. Due to recruitment constraints, only 46 healthy controls were recruited, limiting successful matching. The final analysis included 90 patients and 44 controls. The patient group (62 males and 28 females) had a mean age of 60.64±9.93 years, while the healthy group (23 males and 21 females) had a mean age of 59.43±5.01 years. We found significant gray matter volume loss in the medial superior frontal gyrus and identified both positive and negative directional connectivity patterns between this region and other areas in the prefrontal cortex (inferior frontal gyrus), temporal regions (superior and middle temporal gyri), limbic structures (insula, cingulate gyrus, and parahippocampus), and precentral. Notably, the causal network in patients with mild deficits was more complex.These findings support the existence of structural diaschisis following subcortical stroke, centered in the prefrontal cortex. This study underscores the importance of brain-wide imaging markers and may contribute to developing brain stimulation targets.

Graphical Abstract

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Excitatory-Inhibitory Homeostasis and Diaschisis: Tying the Local and Global Scales in the Post-stroke Cortex

 No clue. You'll have to ask your doctor.

Excitatory-Inhibitory Homeostasis and Diaschisis: Tying the Local and Global Scales in the Post-stroke Cortex

Francisco Páscoa dos Santos^1,2,3 and Paul F. M. J. Verschure^2,4*

• ¹Eodyne Systems SL, Barcelona, Spain
• ²Laboratory of Synthetic, Perceptive, Emotive and Cognitive Systems (SPECS), Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain
• ³Department of Information and Communications Technologies (DTIC), Universitat Pompeu Fabra (UPF), Barcelona, Spain
• ⁴Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain

Maintaining a balance between excitatory and inhibitory activity is an essential feature of neural networks of the neocortex. In the face of perturbations in the levels of excitation to cortical neurons, synapses adjust to maintain excitatory-inhibitory (EI) balance. In this review, we summarize research on this EI homeostasis in the neocortex, using stroke as our case study, and in particular the loss of excitation to distant cortical regions after focal lesions. Widespread changes following a localized lesion, a phenomenon known as diaschisis, are not only related to excitability, but also observed with respect to functional connectivity. Here, we highlight the main findings regarding the evolution of excitability and functional cortical networks during the process of post-stroke recovery, and how both are related to functional recovery. We show that cortical reorganization at a global scale can be explained from the perspective of EI homeostasis. Indeed, recovery of functional networks is paralleled by increases in excitability across the cortex. These adaptive changes likely result from plasticity mechanisms such as synaptic scaling and are linked to EI homeostasis, providing a possible target for future therapeutic strategies in the process of rehabilitation. In addition, we address the difficulty of simultaneously studying these multiscale processes by presenting recent advances in large-scale modeling of the human cortex in the contexts of stroke and EI homeostasis, suggesting computational modeling as a powerful tool to tie the meso- and macro-scale processes of recovery in stroke patients.

Stroke and Diaschisis

In stroke, disruptions in blood flow in the central nervous system lead to focal lesions in the brain or spinal cord, causing it to be one of the most burdening disorders in economically advantaged countries (Campbell and Khatri, 2020). As a result of such lesions, patients experience a broad range of symptoms, with deficits in motor (e.g., hemiparesis), sensory (e.g., hemianopia) and higher-order cognitive processes (e.g., aphasia, hemispatial neglect) (Musuka et al., 2015; Campbell and Khatri, 2020), even leading to neuropsychiatric deficits such as depression (Towfighi et al., 2017) and dementia (Leys et al., 2005). While some of the effects of stroke can be directly attributed to loss of function of lesioned areas (Siegel et al., 2016), its effects extend beyond the lesioned area involving multiple areas across the cortex, a phenomenon known as diaschisis. The term diaschisis, coined by von Monakow (1914), first pertained to a remote loss in excitability following focal lesion impacting the function of brain areas distant to the lesion. Since, then the topic of diaschisis was further elaborated in the following century (Feeney and Baron, 1986), mainly focusing on changes in excitability affecting the local excitatory-inhibitory (EI) balance of distant cortical networks. However, the measurable effects of stroke are not limited to the mesoscale of disruptions in EI balance, extending into large-scale cortical dynamics, such as functional interactions between distant regions. Therefore, extensions to the concept of diaschisis have been proposed in recent years, suggesting remote disruptions in functional connectivity as a relevant aspect of the process (Campo et al., 2012; Carrera and Tononi, 2014). With this recent expansion, attempting to bridge these two types of diaschisis emerging on different spatial scales is, therefore, a relevant issue, not only to better understand possible common physiological causes, but also to inform therapeutical strategies, thus improving post-stroke recovery. That said, in this review, we summarize the main findings related to diaschisis, both regarding functional connectivity (FC) and excitability, and link long-term changes in excitability to cortical plasticity mechanisms related to EI homeostasis, suggesting that the effects of these local processes extend beyond the scale of local EI balance regulation, into large-scale network dynamics. In addition, we summarize the recent advances in computational modeling of stroke, proposing modeling as a framework for the study of the concurrent evolution of FC and excitability in the post-stroke brain.

More at link.

 

A novel therapeutic target for recovery after stroke

Shit this just sounds like the combination of three already known theories of the

neuronal cascade of death.

Or maybe you want to read about this research way back in September 1999?

The Role of Diaschisis in Stroke Recovery March 2018

 

Now we just need our non-existent stroke leadership to get research going to solve these neuron killer processes. That will never occur. WE HAVE NO STROKE LEADERSHIP!

1. Capillaries that don't open due to pericytes  

2. glutamate poisoning
 

3. excitotoxicity

The latest here:

A novel therapeutic target for recovery after stroke

by Institute for Basic Science

Stroke affects not only the brain areas where the blood supply is interrupted or reduced (infarct), but also other distal areas (diaschisis). The researchers studied mouse brains and found that diaschisis is due to the excessive production of the neurotransmitter GABA and that the administration of KDS2010 combined with rehabilitation can improve motor function after stroke. Credit: IBS

Researchers at the Center for Cognition and Sociality, within the Institute for Basic Science (IBS), Gwangju Institute of Science and Technology (GIST), and Korea Institute of Science and Technology (KIST) have discovered a new mechanism to explain the effects of subcortical strokes and a new possible therapeutic approach.

Every year, 15 million people worldwide suffer from stroke according to the World Health Organization. Five million of those die and another five million are permanently disabled. Stroke is one of the most commonly reported causes of death and greatly impacts patients' quality of life. However, despite its prevalence and negative impact, there are no direct medical treatments for recovery after stroke and patients rely on rehabilitation.
A stroke occurs when the blood supply is interrupted or reduced due to bleeding or occlusion of blood vessels in some part of the brain. Brain cells subsequently begin to die within minutes, causing a regional brain damage. In addition, the stroke leads to a loss of function, called diaschisis, in other brain regions connected to the damaged area. Proposed 115 years ago, diaschisis worsens symptoms and prognosis of stroke patients. However, despite broad clinical interest, diaschisis' molecular and cellular mechanisms are still unknown.
In this study, the researchers reported that diaschisis in the cortex of the mouse brain with subcortical stroke is caused by the decline of neuronal activity, due to the reduction in neuronal glucose uptake. They showed that this is dependent on pathological changes of astrocytes, the most abundant cell type in the brain. "Astrocytes respond to the presence of any chemical disregulation, caused by stroke. They become reactive, proliferate and increase in size," says C. Justin Lee, Director of the Cognitive Glioscience Group, at the IBS Center for Cognition and Sociality and co-corresponding author of this research. The researchers discovered that reactive astrocytes synthesize and release an excessive amount of GABA, an inhibitory neurotransmitter, that affects the activity of neighboring motor neurons.

Using Imaging Techniques to Assess the Effects of a Stroke

Wrong, wrong, wrong. You should be using imaging to diagnose all the damage(dead and dying neurons), then map protocols to recover from such damage. This is so fucking easy to understand, why isn't it being done? No protocols is not a valid answer. Lots of words here but nothing useful for recovery.
https://www.news-medical.net/whitepaper/20180626/Using-Imaging-Techniques-to-Assess-the-Effects-of-a-Stroke.aspx

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Sponsored Content by Bruker BioSpin - NMR, EPR and ImagingJun 26 2018

Cerebral ischaemia

Cerebral ischaemia is a type of stroke causing high rates of disability and mortality¹. It occurs when blood vessels serving the brain become blocked or burst. This prevents the affected area of the brain from receiving sufficient oxygen and nutrients to meet its metabolic demands.

© sfam_photo/Shutterstock.com

Consequently, cells in the affected area cannot work properly and the bodily functions for which they are responsible are impaired. Cerebral ischaemia can affect a specific localised area of the brain or be more widespread.
Symptoms of cerebral ischaemia may be fleeting if the interruption of blood supply to the brain is restored quickly, but if oxygen deprivation is prolonged the affected brain tissue will die causing irreversible brain damage. Cerebral ischaemia symptoms include sight disturbances, dizziness, loss of co-ordination, muscle weakness or paralysis, and difficulty speaking.

Changes in the brain after cerebral ischaemia

Cerebral ischaemia results in changes in energy usage, disruption to the metabolism of neurotransmitters and lipids and alterations to protein synthesis. In addition, intracellular cytosolic calcium concentration increases, as does the level of damaging free radicals. It is these metabolic, biochemical and ionic perturbations that ultimately cause neuronal death. Understanding the precise nature of these changes may therefore help in treatments to minimise the debilitating  consequences of a stroke. However, since such a wide range of metabolites is affected, leading to disruption of several complex pathways, unravelling the effects of cerebral ischaemia is not straightforward.
Furthermore, it appears that the pathological changes of stroke may be even more far-reaching than initially thought. Research indicates that metabolic changes occur not only in the area of the brain that has become ischaemic but may also induce secondary effects in other areas of the brain. Such functional impairment of the brain at a location removed from the injury site is known as diaschisis, which appears to be a form of shock response.
Defining and understanding the metabolic disturbances caused by oxygen and nutrient deprivation have this been identified as key to the development of treatments to minimise morbidity in patients suffering cerebral ischaemia². With the possibility of diaschisis, the physiological effects of cerebral ischaemia must be evaluated across the brain and not just in the ischaemic area.
Magnetic resonance imaging and positron emission tomography have successfully measured remote metabolic changes after cerebral ischaemia. Such techniques have provided insight into the more far-reaching effects of stroke in areas of the brain far-removed from the ischaemic area. However, although cerebellar diaschisis has been well studied³, there are few data relating to the less common interhemispheric diaschisis. It remains unclear whether ischaemic damage in one hemisphere can lead to diaschisis in another hemisphere.

Measuring metabolic changes

Metabolomics is the study of biochemical pathways through the measurement of the metabolites. By determining the relative changes in concentration of substrate and product metabolites, it can be inferred whether specific pathways have been up or down-regulated. This methodology has been widely used across a range of disciplines to investigate the effects of drugs or contaminants.
Nuclear magnetic resonance spectroscopy detects molecules based on their chemical shift on application of a magnetic field. Since different types of molecules give different spectral peaks, it can measure the many different components in a complex mixture. It has been widely used to investigate the pathological mechanisms of cerebral ischaemia, but has not to study the effects on biochemical processes within the brain.

Investigating inter-hemisphere effects of cerebral ischemia

A recent study investigated metabolite changes after cerebral artery occlusion in both the left and right cerebral hemispheres of rats⁴. In order to simultaneously measure the quantities of numerous metabolites, ¹H nuclear magnetic resonance (¹H NMR) spectroscopy was employed for the analysis using a Bruker AVANCE III 600 MHz NMR spectrometer. Characteristic changes in metabolites indicated that biochemical changes had occurred in both the ischaemic and contralateral cerebral hemispheres.
In the ischaemic cerebral hemisphere, the changes in metabolites after cerebral ischaemia indicated an increase in anaerobic glycolysis, a perturbation of choline metabolism, neuronal cell damage and neurotransmitter imbalance. In the contralateral hemisphere, an increase in anaerobic glycolysis was also observed, along with changes in energy metabolism and alteration in the balance of neurotransmitters. Since the two cerebral hemispheres are connected by a large mass of neural fibres called the corpus callosum, it is likely that this is the means by which ischaemic damage in one hemisphere can initiate metabolic changes in the other hemisphere.
These findings indicate that interhemispheric diaschisis can indeed occur after cerebral ischaemia. Furthermore, they support cerebral metabolic analysis as valuable tool for understanding the biochemical mechanisms of cerebral ischaemia and its effects on distant areas of the brain.

References

1. Anuncibay-Soto B, et al. Neuroprotection by salubrinal treatment in global cerebral ischemia. Neural Regen Res 2016;11:1744‑1745.
2. Yang M, et al. NMR analysis of the rat neurochemical changes induced by middle cerebral artery occlusion. Talanta 2012;88:136‑144.
3. Madai VI, et al. Crossed cerebellar diaschisis after stroke: can perfusion-weighted MRI show functional inactivation? J Cereb Blood Flow Metab 2011;31:1493‑1500.
4. Ruan L, et al. Metabolite changes in the ipsilateral and contralateral cerebral hemispheres in rats with middle cerebral artery occlusion. Neural Regen Res 2017;12(6):931-937.