Acute ischemic stroke treatment

Acute ischemic stroke treatment

As the second-leading cause of death, stroke faces several challenges in terms of treatment because of the limited therapeutic interventions available. Previous studies primarily focused on metabolic and blood flow properties as a target for ischemic stroke treatment, including recombinant tissue plasminogen activator and mechanical thrombectomy, which are the only USFDA approved therapies. These interventions have the limitation of a narrow therapeutic time window, the possibility of hemorrhagic complications, and the expertise required for performing these interventions. Thus, it is important to identify the contributing factors that exacerbate the acute ischemic stroke outcome and to develop therapies targeting them for regulating cellular homeostasis, mainly neuronal survival and regeneration. Glial cells, primarily microgliaastrocytes, and oligodendrocytes, have been shown to have a crucial role in the prognosis of ischemic brain injury, contributing to inflammatory responses. They play a dual role in both the onset as well as resolution of the inflammatory responses. Understanding the different mechanisms driving these effects can aid in the development of therapeutic targets and further mitigate the damage caused. In a review, Jadhav et al. summarize the functions of various glial cells and their contribution to stroke pathology. The review highlights the therapeutic options currently being explored and developed that primarily target glial cells and can be used as neuroprotective agents for the treatment of ischemic stroke 1).


In the complete absence of blood flowneuronal death occurs within 2–3 minutes from the exhaustion of energy stores. However, in most strokes, there is a salvageable penumbra (tissue at risk) that retains viability for a period of time through suboptimal perfusion from collaterals. Local cerebral edema from the stroke results in a compromise of these collaterals and progression of the ischemic penumbra to infarction if the flow is not restored and maintained. Prevention of this secondary neuronal injury drives the treatment of stroke and has led to the creation of designated Primary Stroke Centers that offer appropriate and timely triage and treatment of all potential stroke patients.

Time delays from initial CTA acquisition to neuroendovascular surgery (NES) team notification can prevent expedient treatment with endovascular thrombectomy (ET). Process improvements and automated stroke detection on imaging with automated notification of the NES team may ultimately improve the time to reperfusion 2).

Restoring the circulation is the primary goal in emergency cerebral ischemia treatment. However, better understanding of how the brain responds to energy depletion could inform the time available for resuscitation until irreversible damage and advance development of interventions that prolong this span.


Finding novel agent for cerebral ischemia therapy is urgently required. In a study, Gao et al., aimed to investigate the regulatory mechanism of Ginkgolides B (GB) in hypoxia-injured PC-12 cells.

PC-12 cells were exposed to hypoxia and administrated with GB. Cell viability was detected by MTT assay. Flow cytometry assay was conducted for the detection of cell apoptosis, ROS generation and cell cycle assay. The changes of protein levels of Bax, Pro/Cleaved-Caspase-3, CyclinD1, CDK4, CDK6, PI3K/AKT and MEK/ERK pathways were detected by Western blot. Transfection was conducted for Polo-like kinase 1 (PLK1) knockdown.

Hypoxia-induced decrease of cell viability and increase of ROS generation, apoptosis and cell cycle arrest were ameliorated by GB. Hypoxia disposition hindered PI3 K/AKT and MEK/ERK signaling pathways while GB had the opposite effects. Then we observed that hypoxia exposure suppressed PLK1 expression while GB increased PLK1 expression dose-dependently. Knockdown of PLK1 attenuated the neuroprotective effects of GB on hypoxia-injured PC-12 cells and also inhibited PI3 K/AKT and MEK/ERK pathways.

The above observations corroborated that GB alleviated hypoxia-induced PC-12 cell injury by up-regulation of PLK1 via activating PI3K/AKT and MEK/ERK pathways. These findings implied the neuro-protective impacts in hypoxia-injured PC-12 cells 3).

see also Cerebral venous sinus thrombosis treatment.


Remarkable developments in the field of endovascular neurosurgery have been witnessed in the last decade. The success of endovascular therapy for ischemic stroke treatment is now irrefutable, making it an accepted standard of care 4).

In ischemic stroke or patients with TIA less than five cerebral microbleeds (CMBs) should not affect antithrombotic decisions, although with more than five CMBs the risks of future ICH and ischaemic stroke are finely balanced, and antithrombotics might cause net harm. In lobar ICH populations, a high burden of strictly lobar CMBs is associated with cerebral amyloid angiopathy (CAA) and high ICH risk; antithrombotics should be avoided unless there is a compelling indication 5).

Intravenous recombinant human tissue plasminogen activator for ischemic stroke treatment.

Endovascular intervention for ischemic stroke treatment.

American Heart Association Guidelines for the Early Management of Patients With Acute Ischemic Stroke

see Hypothermia for acute ischemic stroke treatment.


Brain ischemia and treatment are one of the important topics in neurological science. Free oxygen radicals and inflammation formed after ischemia are accepted as the most important causes of damage. Currently, there are studies on many chemopreventive agents to prevent cerebral ischemia damage. The aim of Aras et al is to research the preventive effect of the active ingredient in genistein There is currently no promising pharmacotherapy aside from intravenous or intra-arterial thrombolysis. Yet because of the narrow therapeutic time window involved, thrombolytic application is very restricted in clinical settings. Accumulating data suggest that non-pharmaceutical therapies for stroke might provide new opportunities for stroke treatment 6).

Progression of focal stroke symptoms still constitutes a serious clinical problem for which heparin has insufficient effectiveness in clinical practice. New therapies, ideally preventive, are needed 7).

Omega 3 fatty acid enhance cerebral angiogenesis and provide long-term protection after stroke 8).

After cerebral ischemia, revascularization in the ischemic boundary zone provides nutritive blood flow as well as various growth factors to promote the survival and activity of neurons and neural progenitor cells. Enhancement of angiogenesis and the resulting improvement of cerebral microcirculation are key restorative mechanisms and represent an important therapeutic strategy for ischemic stroke.

Improvements in acute ischemic stroke (AIS) outcomes have been achieved with intravenous thrombolytics (IVT) and intra-arterial thrombolytics vs supportive medical therapy. Given its ease of administration, noninvasiveness, and most validated efficacy, IVT is the standard of care in AIS patients without contraindications to systemic fibrinolysis. However, patients with large-vessel occlusions respond poorly to IVT. Recent trials designed to select this population for randomization to IVT vs IVT with adjunctive endovascular therapy have not shown improvement in clinical outcomes with endovascular therapy. This could be due to the lack of utilization of modern thrombectomy devices such as Penumbra aspiration devices, Solitaire stent-trievers, or Trevo stent-trievers, which have shown the best recanalization results. Continued improvement in the techniques with using these devices as well as randomized controlled trials using them is warranted 9).

With the emergence of new technologies in imaging, thrombolysis and endovascular intervention, the treatment modalities of acute ischemic stroke will enter a new era 10).

Within 3 h from symptom onset, the existence of FLAIR-positive lesions on pretreatment MRI is significantly associated with an increased bleeding risk due to systemic thrombolysis. Therefore, considering FLAIR-positive lesions on baseline MRI might guide treatment decisions in ischemic stroke 11).

see Acute ischemic stroke thrombolysis

see Blood Pressure Management.

Intensive rehabilitation effectively improves physical functions in patients with acute stroke, but the frequency of intervention and its cost-effectiveness are poorly studied. This study aimed to examine the effect of early high-frequency rehabilitation intervention on inpatient outcomes and medical expenses of patients with stroke.

Methods: The study retrospectively included 1759 patients with acute stroke admitted to the Kobe City Medical Center General Hospital between 2013 and 2016. Patients with a transient ischemic attack, subarachnoid hemorrhage, and those who underwent urgent surgery were excluded. Patients were divided into two groups according to the frequency of rehabilitation intervention: the high-frequency intervention group (>2 times/day, n = 1105) and normal-frequency intervention group (<2 times/day, n = 654). A modified Rankin scale score ≤2 at discharge, immobility-related complications and medical expenses were compared between the groups.

Results: The high-frequency intervention group had a significantly shorter time to first rehabilitation (median [interquartile range], 19.0 h [13.1-38.4] vs. 24.7 h [16.1-49.4], P < 0.001) and time to first mobilization (23.3 h [8.7-47.2] vs. 22.8 h [5.7-62.3], P = 0.65) than the normal-frequency intervention group. Despite higher disease severity, the high-frequency intervention group exhibited favorable outcomes at discharge (modified Rankin scale, ≤2; adjusted odds ratio, 1.89; 95% confidence interval, 1.25-2.85; P = 0.002). No significant differences were observed between the two groups concerning the rate of immobility-related complications and total medical expenses during hospitalization.

Conclusions: High-frequency intervention was associated with improved outcomes and decreased medical expenses in patients with stroke. Our results may contribute to reducing medical expenses by increasing the efficiency of care delivery 12).


1)

Jadhav P, Karande M, Sarkar A, Sahu S, Sarmah D, Datta A, Chaudhary A, Kalia K, Sharma A, Wang X, Bhattacharya P. Glial Cells Response in Stroke. Cell Mol Neurobiol. 2022 Jan 23. doi: 10.1007/s10571-021-01183-3. Epub ahead of print. PMID: 35066715.
2)

Yaeger KA, Rossitto CP, Marayati NF, Lara-Reyna J, Ladner T, Hardigan T, Shoirah H, Mocco J, Fifi JT. Time from image acquisition to endovascular team notification: a new target for enhancing acute stroke workflow. J Neurointerv Surg. 2021 Apr 8:neurintsurg-2021-017297. doi: 10.1136/neurintsurg-2021-017297. Epub ahead of print. PMID: 33832969.
3)

Gao J, Kang M, Han Y, Zhang T, Jin H, Kang C. Ginkgolides B alleviates hypoxia-induced PC-12 cell injury by up-regulation of PLK1. Biomed Pharmacother. 2019 Apr 25;115:108885. doi: 10.1016/j.biopha.2019.108885. [Epub ahead of print] PubMed PMID: 31029888.
4)

Levy EI, Munich SA, Rosenwasser RH, Kan P, Thompson BG. Introduction: Endovascular Neurosurgery. Neurosurg Focus. 2019 Jan 1;46(Suppl_1):V1. doi: 10.3171/2019.1.FocusVid.Intro. PubMed PMID: 30611172.
5)

Wilson D, Werring DJ. Antithrombotic therapy in patients with cerebral microbleeds. Curr Opin Neurol. 2016 Nov 24. [Epub ahead of print] PubMed PMID: 27898582.
6)

Chen F, Qi Z, Luo Y, Hinchliffe T, Ding G, Xia Y, Ji X. Non-pharmaceutical therapies for stroke: Mechanisms and clinical implications. Prog Neurobiol. 2014 Jan 6. pii: S0301-0082(13)00147-0. doi: 10.1016/j.pneurobio.2013.12.007. [Epub ahead of print] PubMed PMID: 24407111.
7)

Rödén-Jüllig A, Britton M. Effectiveness of heparin treatment for progressing ischaemic stroke: before and after study. J Intern Med. 2000 Oct;248(4):287-91. PubMed PMID: 11086638.
8)

Wang J, Shi Y, Zhang L, Zhang F, Hu X, Zhang W, Leak RK, Gao Y, Chen L, Chen J. Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke. Neurobiol Dis. 2014 Apr 29. pii: S0969-9961(14)00103-X. doi: 10.1016/j.nbd.2014.04.014. [Epub ahead of print] PubMed PMID: 24794156.
9)

Serrone JC, Jimenez L, Ringer AJ. The role of endovascular therapy in the treatment of acute ischemic stroke. Neurosurgery. 2014 Feb;74 Suppl 1:S133-41. doi: 10.1227/NEU.0000000000000224. PubMed PMID: 24402482.
10)

Lu AY, Ansari SA, Nyström KV, Damisah EC, Amin HP, Matouk CC, Pashankar RD,Bulsara KR. Intra-arterial treatment of acute ischemic stroke: the continued evolution. Curr Treat Options Cardiovasc Med. 2014 Feb;16(2):281. doi:10.1007/s11936-013-0281-2. PubMed PMID: 24398801.
11)

Hobohm C, Fritzsch D, Budig S, Classen J, Hoffmann KT, Michalski D. Predicting intracerebral hemorrhage by baseline magnetic resonance imaging in stroke patients undergoing systemic thrombolysis. Acta Neurol Scand. 2014 Jul 18. doi: 10.1111/ane.12272. [Epub ahead of print] PubMed PMID: 25040041.
12)

Oyanagi K, Kitai T, Yoshimura Y, Yokoi Y, Ohara N, Kohara N, Sakai N, Honda A, Onishi H, Iwata K. Effect of early intensive rehabilitation on the clinical outcomes of patients with acute stroke. Geriatr Gerontol Int. 2021 Jun 8. doi: 10.1111/ggi.14202. Epub ahead of print. PMID: 34101957.

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