Treating Cerebral Ischemia: Novel Therapeutic Strategies from Experimental Stroke Research

Zheng, Xuan; Haupt, Matteo; Bähr, Mathias; Tatenhorst, Lars; Doeppner, Thorsten R.

doi:10.36255/exonpublications.cerebralischemia.2021.therapy

Cited by 7 publications

(7 citation statements)

References 137 publications

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“…Using tissue plasminogen activator (tPA) to treat stroke patients is the current therapeutic strategy. However, tPA treatment confronts ill side effects, such as tPA is limited to stroke patients within 4.5 h of stroke incidence and increases the danger of cerebral bleeding and brain damage, thus limiting their usage in clinical settings [ 19 ]. Owing to the difficulties associated with tPA, it is necessary to consider other safe and efficacious strategies for stroke.…”

Section: Discussionmentioning

confidence: 99%

Protection of Gueichih-Fuling-Wan on cerebral ischemia-induced brain injury in rodents is mediated by trans-cinnamaldehyde via inhibition of neuroinflammation and apoptosis

Chen,

Wu,

Kuo

et al. 2024

BioMedicine

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Background Stroke is the leading cause of mortality and morbidity worldwide, and an effective therapeutic strategy for the prevention of patients with cerebral ischemia induced brain injury is lacking. Traditional Chinese medicine with neuroprotective activities might be beneficial and provide alternative therapeutic opportunities for cerebral ischemia. Purposes This study aimed to evaluate the neuroprotection and possible mechanisms of Gueichih-Fuling-Wan (GFW), its’ constitutive herbs, and their active compounds on cerebral ischemia/reperfusion (I/R)-induced brain injury in rodents. Methods Various doses of extracts (0.25, 0.5, and 1.0 g/kg) of GFW and five constituent herbs ( Cinnamomi Cortex , CC; Poria cocos , PC; Paeonia lactifloa , PL; Paeonia suffruticosa , PS and Prunus perisica , PP) were orally administered. Different doses of active compounds (0.5, 1.0, and 2.0 mg/kg) of GFW such as cinnamaldehyde, cinnamic acid (from CC), paeoniflorin (from PL), and paeonol (from PS) were intraperitoneally administered. Their effects on cerebral ischemia/ reperfusion (I/R)induced brain injury in rodents were evaluated. Results GFW, its’ constituent herbs, and the active compounds reduced the infarct area dose-dependently (***P < 0.001). Cinnamaldehyde showed the most significant reduction (***P < 0.001). Therefore, trans-cinnamaldehyde (TCA) was further used to evaluate the neuroprotective mechanism of the I/R-induced brain injury. TCA (10, 20, 30 mg/ kg, p.o.) showed an inhibitory effect of I/R-induced brain damage in mice in a dose-dependent manner. Besides, GFW and TCA dose-dependently reduced the COX-2 protein expression level, and TCA reduced the TUNEL (+) apoptosis. TCA dose-dependently increased the pro-survival NR2A and Bcl-2 protein expression level and decreased the pro-apoptotic NR2B and cytochrome c , caspase 9, and caspase 3 expression (***P < 0.001). Conclusion The above data revealed that GFW, its’ constituent herbs, and active compounds protected against I/R-induced brain injury in rodents. TCA from CC might participate in GFW protecting against cerebral ischemia-induced brain injury by inhibiting neuroinflammation and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Protection of Gueichih-Fuling-Wan on cerebral ischemia-induced brain injury in rodents is mediated by trans-cinnamaldehyde via inhibition of neuroinflammation and apoptosis

Chen,

Wu,

Kuo

et al. 2024

BioMedicine

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“…These small membrane-encapsulated vesicles in the range of nanometers have gained increasing interest in recent years; EVs have been demonstrated to be non-inferior to their host stem cells with regard to their therapeutic potential against stroke [27]. EVs serve as cargo carriers for nucleic acids, proteins and lipids, all of which affect stroke outcomes in their own specific ways [28]. However, EV contents depend on the state of host cell functioning, which determines different metabolic patterns of secreted EVs.…”

Section: Preclinical Studies-a Brief Overviewmentioning

confidence: 99%

Quest for Quality in Translational Stroke Research—A New Dawn for Neuroprotection?

Haupt

Gerner

Bähr

et al. 2022

IJMS

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Despite tremendous progress in modern-day stroke therapy, ischemic stroke remains a disease associated with a high socioeconomic burden in industrialized countries. In light of demographic change, these health care costs are expected to increase even further. The current causal therapeutic treatment paradigms focus on successful thrombolysis or thrombectomy, but only a fraction of patients qualify for these recanalization therapies because of therapeutic time window restrictions or contraindications. Hence, adjuvant therapeutic concepts such as neuroprotection are urgently needed. A bench-to-bedside transfer of neuroprotective approaches under stroke conditions, however, has not been established after more than twenty years of research, albeit a great many data have demonstrated several neuroprotective drugs to be effective in preclinical stroke settings. Prominent examples of substances supported by extensive preclinical evidence but which failed clinical trials are tirilazad and disodium 2,4-sulphophenyl-N-tert-butylnitrone (NXY-059). The NXY-059 trial, for instance, was retrospectively shown to have a seriously weak study design, a trial of insufficient quality and a poor statistical analysis, although it initially met the recommendations of the STAIR committee. In light of currently ongoing novel neuroprotective stroke trials, such as ESCAPE-NA, and to avoid the mistakes made in the past, an improvement in study quality in the field of stroke neuroprotection is urgently needed. In the present review, animal models closely reflecting the “typical” stroke patient, occlusion techniques and the appropriate choice of time windows are discussed. In this context, the STAIR recommendations could provide a useful orientation. Taking all of this into account, a new dawn for neuroprotection might be possible.

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“…Lithium may reverse the grey matter atrophy by stimulating neurogenesis [24]. Several neuroprotective agents, including lithium, have been shown to stabilize the blood-brain barrier (BBB) as part of their neuroprotective mechanisms [25]. The endothelium is a critical component of the BBB function, and it plays a role in regulating its properties.…”

Section: Ischemic Stroke Pathological Context and Lithium Interventionsmentioning

confidence: 99%

Lithium Biological Action Mechanisms after Ischemic Stroke

Munteanu

Rotariu

Turnea

et al. 2022

Life

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Lithium is a source of great scientific interest because although it has such a simple structure, relatively easy-to-analyze chemistry, and well-established physical properties, the plethora of effects on biological systems—which influence numerous cellular and molecular processes through not entirely explained mechanisms of action—generate a mystery that modern science is still trying to decipher. Lithium has multiple effects on neurotransmitter-mediated receptor signaling, ion transport, signaling cascades, hormonal regulation, circadian rhythm, and gene expression. The biochemical mechanisms of lithium action appear to be multifactorial and interrelated with the functioning of several enzymes, hormones, vitamins, and growth and transformation factors. The widespread and chaotic marketing of lithium salts in potions and mineral waters, always at inadequate concentrations for various diseases, has contributed to the general disillusionment with empirical medical hypotheses about the therapeutic role of lithium. Lithium salts were first used therapeutically in 1850 to relieve the symptoms of gout, rheumatism, and kidney stones. In 1949, Cade was credited with discovering the sedative effect of lithium salts in the state of manic agitation, but frequent cases of intoxication accompanied the therapy. In the 1960s, lithium was shown to prevent manic and also depressive recurrences. This prophylactic effect was first demonstrated in an open-label study using the “mirror” method and was later (after 1970) confirmed by several placebo-controlled double-blind studies. Lithium prophylaxis was similarly effective in bipolar and also unipolar patients. In 1967, the therapeutic value of lithemia was determined, included in the range of 0.5–1.5 mEq/l. Recently, new therapeutic perspectives on lithium are connected with improved neurological outcomes after ischemic stroke. The effects of lithium on the development and maintenance of neuroprotection can be divided into two categories: short-term effects and long-term effects. Unfortunately, the existing studies do not fully explain the lithium biological action mechanisms after ischemic stroke.

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Treating Cerebral Ischemia: Novel Therapeutic Strategies from Experimental Stroke Research

Cited by 7 publications

References 137 publications

Protection of Gueichih-Fuling-Wan on cerebral ischemia-induced brain injury in rodents is mediated by trans-cinnamaldehyde via inhibition of neuroinflammation and apoptosis

Protection of Gueichih-Fuling-Wan on cerebral ischemia-induced brain injury in rodents is mediated by trans-cinnamaldehyde via inhibition of neuroinflammation and apoptosis

Quest for Quality in Translational Stroke Research—A New Dawn for Neuroprotection?

Lithium Biological Action Mechanisms after Ischemic Stroke

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