Diaschisis, Degeneration, and Adaptive Plasticity After Focal Ischemic Stroke

Sist, Bernice; Jesudasan, Sam Joshva Baskar; Winship, Ian R.

doi:10.5772/28577

Cited by 8 publications

(7 citation statements)

References 198 publications

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“…26 This framework also suggests that post-stroke phenomena such as functional diaschisis and secondary neurodegeneration drive increases in apathy over time. 27 These phenomena can occur distal to an acute infarct, leading to clinical symptoms that appear inconsistent or unexpected if only considering a focal lesion. Importantly, secondary neurobiological changes can propagate through structural and functional connections within the brain, potentially leading to apathy if affecting GDB-related networks (Figure 2).…”

Section: Neurobiological Mechanisms Underlying Apathymentioning

confidence: 99%

“…As a corollary, apathy may improve in response to restorative mechanisms such as adaptive plasticity and functional remapping. 27 The anterior cingulate cortex (ACC) and nucleus accumbens may be core network regions supporting GDB, as damage to these structures is associated with apathy across neurological disorders. 28 These core regions are embedded in large-scale functionally connected networks that underlie GDB-related cognitive functions such as reward-based decision-making, attentional control, and reinforcement learning.…”

Section: Neurobiological Mechanisms Underlying Apathymentioning

confidence: 99%

“…As a corollary, apathy may improve in response to restorative mechanisms such as adaptive plasticity and functional remapping. 27

Figure 2.A network-based model of how stroke leads to apathy. Apathy can result from focal lesions disrupting key network regions or from diffuse damage such as white matter ischemia.…”

Section: Neurobiological Mechanisms Underlying Apathymentioning

confidence: 99%

“…As a corollary, apathy may improve in response to restorative mechanisms such as adaptive plasticity and functional remapping. 27

Figure 2. A network-based model of how stroke leads to apathy.…”

Section: Neurobiological Mechanisms Underlying Apathymentioning

confidence: 99%

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Apathy after stroke: Diagnosis, mechanisms, consequences, and treatment

Tay

Morris

Markus

2021

International Journal of Stroke

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Apathy is a reduction in goal-directed activity in the cognitive, behavioural, emotional, or social domains of a patient's life, and occurs in one out of three patients after stroke. Despite this, apathy is clinically under-recognised and poorly understood. This overview provides a contemporary introduction to apathy in stroke for researchers and practitioners, covering topics including diagnosis, neurobiological mechanisms, associated consequences, and potential treatments for apathy. Apathy is often misdiagnosed as other post-stroke conditions such as depression. Accurate differential diagnosis of apathy, which manifests as reductions in initiative, and depression, which manifests as negative emotionality, is important as it informs prognosis. Research on the neurobiology of apathy suggests that there are few consistent associations between stroke lesion location and the development of apathy. These may be resolved by adopting a network neuroscience approach, which conceptualises of apathy as a pathology arising from structural or functional damage to brain networks underlying motivated behaviour. Importantly, networks can be affected by physiological changes related to stroke, including the acute infarct but also diaschisis and neurodegeneration. Aside from neurobiological changes, apathy is also associated with other negative outcome measures such as functional disability, cognitive impairment, and emotional distress, suggesting that apathy is indicative of a worse prognosis following stroke. Unfortunately, high-quality trials aimed at treating apathy are scarce. Antidepressants may have limited effects on apathy. Acetylcholine and dopamine pharmacotherapy, behavioural interventions, and transcranial magnetic stimulation may be more promising avenues for treatment.

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Section: Neurobiological Mechanisms Underlying Apathymentioning

confidence: 99%

Section: Neurobiological Mechanisms Underlying Apathymentioning

confidence: 99%

“…As a corollary, apathy may improve in response to restorative mechanisms such as adaptive plasticity and functional remapping. 27

Figure 2.A network-based model of how stroke leads to apathy. Apathy can result from focal lesions disrupting key network regions or from diffuse damage such as white matter ischemia.…”

Section: Neurobiological Mechanisms Underlying Apathymentioning

confidence: 99%

“…As a corollary, apathy may improve in response to restorative mechanisms such as adaptive plasticity and functional remapping. 27

Figure 2. A network-based model of how stroke leads to apathy.…”

Section: Neurobiological Mechanisms Underlying Apathymentioning

confidence: 99%

See 2 more Smart Citations

Apathy after stroke: Diagnosis, mechanisms, consequences, and treatment

Tay

Morris

Markus

2021

International Journal of Stroke

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“…8,9 We believe that ischemia can alter the expression of class II HDACs and nuclear shuttling of HDACs, which are known to be involved in neurogenesis, and that they can be involved in the recovery after the injury. 10,11 Therefore, on the model of focal cerebral ischemia in mice we studied whether stroke alters expression and nuclear shuttling of HDACs in neurons and astrocytes in these regions of brain. It is obvious that endogenous mechanisms are insufficient for complete recovery of neurological functions, however, preclinical data in rodents indicate that enhancement of endogenous brain recovery can improve the functional state after stroke.…”

mentioning

confidence: 99%

Сlass II histone deacetylases in the post‐stroke recovery period—expression, cellular, and subcellular localization—promising targets for neuroprotection

Demyanenko

Berezhnaya

Neginskaya

et al. 2019

J of Cellular Biochemistry

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Histone deacetylases (HDAC) inhibitors can protect nerve cells after a stroke, but it is unclear which HDAC isoform is involved in this effect. We studied cellular and intracellular rearrangement of class II HDACs at late periods after photothrombotic infarct (PTI) in the mouse sensorimotor cortex in the tissue surrounding the ischemia core and in the corresponding region of the contralateral hemisphere. We observed a decrease in HDAC4 in cortical neurons and an increase in its nuclear translocation. HDAC6 expression in neurons was also increased. Moreover, HDAC6-positive cells had elevated apoptosis. Tubostatin A (Tub A)-induced decrease in the activity of HDAC6 restored acetylation of α-tubulin during the early poststroke recovery period and reduced apoptosis of nerve cells thus protecting the brain tissue. Selective inhibition of HDAC6 elevated expression of growth-associated protein-43 (GAP43), which remained high up to 14 days after stroke and promoted axogenesis and recovery from the PTI-induced neurological deficit. Selective HDAC6 inhibitor Tub A markedly reduced neuronal death and increased acetylation of α-tubulin and the level of GAP43. Thus, HDAC6 inhibition could be a promising strategy for modulation of brain recovery as it can increase the intensity and reduce the duration of reparation processes in the brain after stroke. K E Y W O R D Sbrain regeneration, class II histone deacetylases, cortex, HDAC6, photothrombotic infarction, stroke, Tubastatin A

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