Comparison between single and combined post-treatment with S-Methyl-N,N-diethylthiolcarbamate sulfoxide and taurine following transient focal cerebral ischemia in rat brain

Gharibani, Payam; Modi, Jigar; Menzie, Janet; Alexandrescu, Anamaria; Ma, Z.; Tao, Rui; Prentice, Howard; Wu, Jang‐Yen

doi:10.1016/j.neuroscience.2015.05.042

Cited by 40 publications

(34 citation statements)

References 77 publications

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“…Brain tissues derived from the rats subjected to sham, I/R and IR/+rhMG53 were assayed for changes in caspase3 enzymatic activity as an indicator of apoptotic cell death (Figure 4d). Consistent with studies from other investigators [18–20], we found that I/R-induced brain injury led to activation of caspase3 activity; and rhMG53 treatment could suppress caspase3 activation (Figure 4d and 4e). Together, these results suggest that the reduction of apoptotic cell death contributes to MG53-mediated neuro-protection following I/R injury.…”

Section: Resultssupporting

confidence: 92%

MG53 permeates through blood-brain barrier to protect ischemic brain injury

et al. 2016

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Ischemic injury to neurons represents the underlying cause of stroke to the brain. Our previous studies identified MG53 as an essential component of the cell membrane repair machinery. Here we show that the recombinant human (rh)MG53 protein facilitates repair of ischemia-reperfusion (IR) injury to the brain. MG53 rapidly moves to acute injury sites on neuronal cells to form a membrane repair patch. IR-induced brain injury increases permeability of the blood-brain-barrier, providing access of MG53 from blood circulation to target the injured brain tissues. Exogenous rhMG53 protein can protect cultured neurons against hypoxia/reoxygenation-induced damages. Transgenic mice with increased levels of MG53 in the bloodstream are resistant to IR-induced brain injury. Intravenous administration of rhMG53, either prior to or after ischemia, can effectively alleviate brain injuries in rats. rhMG53-mediated neuroprotection involves suppression of apoptotic neuronal cell death, as well as activation of the pro-survival RISK signaling pathway. Our data indicate a physiological function for MG53 in the brain and suggest that targeting membrane repair or RISK signaling may be an effective means to treat ischemic brain injury.

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Section: Resultssupporting

confidence: 92%

MG53 permeates through blood-brain barrier to protect ischemic brain injury

et al. 2016

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“…Our previous study confirmed that G-CSF has beneficial effects on the protection against ER stress in the penumbra and core of the MCAO infarct [23]. Following detachment of GRP78, PERK is turned on and then phosphorylates a subunit of eIF2a [37] which in turn inhibits general cap-dependent translation thus decreasing further the buildup of proteins within the ER lumen [22,37]. However, PERK activates two down-stream proteins in the PERK pathway of ER stress (namely eIF2-alpha and ATF4).…”

Section: Discussionsupporting

confidence: 71%

“…PERK, IRE-1 and ATF6 all converge on the promoter of the gene encoding the protein CHOP, which controls the BCL-2 family [22,37]. At day 4 a significant drop was observed in CHOP to less than 30 and 50% in front and middle regions respectively relative to vehicle treated BCAO.…”

Section: Resultsmentioning

confidence: 98%

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Mode of action of granulocyte-colony stimulating factor (G-CSF) as a novel therapy for stroke in a mouse model

Modi

Menzie-Suderam

et al. 2020

J Biomed Sci

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Background: The FDA approved drug granulocyte-colony stimulating factor (G-CSF) displays anti-apoptotic and immunomodulatory properties with neurogenesis and angiogenic functions. It is known to demonstrate neuroprotective mechanisms against ischemic global stroke. Autophagy is a method for the degradation of intracellular components and in particular, unrestrained autophagy may lead to uncontrolled digestion of affected neurons as well as neuronal death in cerebral ischemia. Mitochondrial dynamics is vital for the regulation of cell survival and death after cerebral ischemia and an early upstream event in neuronal death is mitochondrial fission. We examined the pro-survival mechanisms of G-CSF against apoptosis resulting from autophagy, mitochondrial stress and endoplasmic reticulum (ER) stress. Methods: Male Swiss Webster mice (20 weeks of age) were subjected to bilateral common carotid artery occlusion (BCAO) for 30 min. After occlusion, mice were injected with G-CSF (50 μg/kg) subcutaneously for 4 days. Behavioral analysis was carried out using the corner test and locomotor activity test before animals were sacrificed on day 4 or day 7. Key proteins in ER stress, autophagy and mitochondrial stress induced apoptosis were analyzed by immunoblotting.Results: G-CSF improved neurological deficits and improved behavioral performance on corner and locomotor test. G-CSF binds to G-CSF receptors and its activation leads to upregulation of Akt phosphorylation (P-Akt) which in turn decreases levels of the ER stress sensor, GRP 78 and expression of proteins involved in ER stress apoptosis pathway; ATF6, ATF4, eIF2α, XBP1, Caspase 12 and CHOP. G-CSF treatment significantly decreased Beclin-1, an autophagy marker, and decreased mitochondrial stress biomarkers DRP1 and P53. G-CSF also up-regulated the mitochondrial fusion protein, OPA1 and anti-apoptotic protein Bcl-2 while down-regulating the pro-apoptotic proteins Bax, Bak and PUMA. Conclusions: G-CSF is an endogenous ligand in the CNS that has a dual activity that is beneficial both in reducing acute neuronal degeneration and adding to long-term plasticity after cerebral ischemia. G-CSF treatment exerts neuroprotective effects on damaged neurons through the suppression of the ER stress and mitochondrial stress and maintains cellular homeostasis by decreasing pro-apoptotic proteins and increasing of anti-apoptotic proteins.

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“…The PERK/eIF2α pathway and its downstream regulators have been shown to be upregulated in studies related to cerebral ischemia [116], recurrent febrile seizures [117], and traumatic brain injury [118], and the involvement of PERK has been previously documented in a brain ischemia and reperfusion model, with the help of eIF2α. [119].…”

Section: Er Stress Components and Ich Therapeutic Strategiesmentioning

confidence: 99%

A Role for Endoplasmic Reticulum Stress in Intracerebral Hemorrhage

Thangameeran

Tsai

Hung

et al. 2020

Cells

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The endoplasmic reticulum (ER) is an intracellular organelle that performs multiple functions, such as lipid biosynthesis, protein folding, and maintaining intracellular calcium homeostasis. Thus, conditions wherein the ER is unable to fold proteins is defined as ER stress, and an inbuilt quality control mechanism, called the unfolded protein response (UPR), is activated during ER stress, which serves as a recovery system that inhibits protein synthesis. Further, based on the severity of ER stress, the response could involve both proapoptotic and antiapoptotic phases. Intracerebral hemorrhage (ICH) is the second most common subtype of cerebral stroke and many lines of evidence have suggested a role for the ER in major neurological disorders. The injury mechanism during ICH includes hematoma formation, which in turn leads to inflammation, elevated intracranial pressure, and edema. a proper understanding of the injury mechanism(s) is required to effectively treat ICH and closing the gap between our current understanding of ER stress mechanisms and ICH injury can lead to valuable advances in the clinical management of ICH.Cells 2020, 9, 750 2 of 20 because of cardiovascular conditions, with hypertension playing a major role. PBI is characterized by mechanical injury followed by a mass effect with the initial ictus causing physical tissue disruption that then leads to pathophysiological conditions in the brain.A sudden rise in intracranial hematoma volume causes an increase in barotrauma and reduces blood flow to the area of the ictus [4,5]. Typically, PBI is followed by SBI, which is considered as a devastating stage after ICH, and the severity of SBI depends on the rate of recovery and location of the ICH. SBI involves the neuroinflammatory response to the triggering of the coagulation cascade through activation of the immune system. The inflammation size is based on the volume and position of the hematoma [5][6][7]. The various pathological factors responsible for SBI include the host immune response, release of thrombin, release of clot components (iron and heme)

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Comparison between single and combined post-treatment with S-Methyl-N,N-diethylthiolcarbamate sulfoxide and taurine following transient focal cerebral ischemia in rat brain

Cited by 40 publications

References 77 publications

MG53 permeates through blood-brain barrier to protect ischemic brain injury

MG53 permeates through blood-brain barrier to protect ischemic brain injury

Mode of action of granulocyte-colony stimulating factor (G-CSF) as a novel therapy for stroke in a mouse model

A Role for Endoplasmic Reticulum Stress in Intracerebral Hemorrhage

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