Deans' stroke musings: Longitudinal Variations of CDC42 in Patients With Acute Ischemic Stroke During 3-Year Period: Correlation With CD4+ T Cells, Disease Severity, and Prognosis

Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Thursday, April 28, 2022

Longitudinal Variations of CDC42 in Patients With Acute Ischemic Stroke During 3-Year Period: Correlation With CD4+ T Cells, Disease Severity, and Prognosis

Useless, you're predicting failure to recover using CDC42 levels. What survivor wants to hear that?

Longitudinal Variations of CDC42 in Patients With Acute Ischemic Stroke During 3-Year Period: Correlation With CD4⁺ T Cells, Disease Severity, and Prognosis

Xiao Cheng^1,2,

Jianxin Ye³^*,

Xiaolei Zhang¹ and

Kun Meng¹

¹Department of Neurology, ShanXi Province People's Hospital of Shanxi Medical University, Taiyuan, China
²Shanxi Key Laboratory of Brain Disease Control, Shanxi Provincial People's Hospital, Taiyuan, China
³Department of Neurology, The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Fuzhou, China

Objective: Cell division cycle 42 (CDC42) modulates CD4⁺ T-cell differentiation, blood lipids, and neuronal apoptosis and is involved in the pathogenesis of acute ischemic stroke (AIS); however, the clinical role of CDC42 in AIS remains unanswered. This study aimed to evaluate the expression of CDC42 in a 3-year follow-up and its correlation with disease severity, T helper (Th)1/2/17 cells, and the prognosis in patients with AIS.

Methods: Blood CDC42 was detected in 143 patients with AIS at multiple time points during the 3-year follow-up period and in 70 controls at admission by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, blood Th1, Th2, and Th17 cells and their secreted cytokines (interferon-γ (IFN-γ), interleukin-4 (IL-4), and interleukin-17A (IL-17A)) in patients with AIS were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively.

Results: Compared with controls (p < 0.001), CDC42 was reduced in patients with AIS. CDC42 was negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score (p < 0.001), whereas, in patients with AIS (all p < 0.050), it was positively associated with Th2 cells and IL-4 but negatively correlated with Th17 cells and IL-17A. CDC42 was decreased from admission to 3 days and gradually increased from 3 days to 3 years in patients with AIS (P<0.001). In a 3-year follow-up, 24 patients with AIS recurred and 8 patients died. On the 3rd day, 7th day, 1st month, 3rd month, 6th month, 1st year, 2nd year, and 3rd year, CDC42 was decreased in recurrent patients than that in non-recurrent patients (all p < 0.050). CDC42 at 7 days (p = 0.033) and 3 months (p = 0.023) was declined in reported deceased patients than in survived patients.

Conclusion: CDC42 is used as a biomarker to constantly monitor disease progression and recurrence risk of patients with AIS.

Introduction

Stroke is a common cerebrovascular disease, which has affected nearly 104 million people worldwide in the past three decades and has climbed to the second leading cause of death (second only to ischemic heart disease), besides, stroke is also known for its high disability rate (nearly 33.4–71%) (1–4). Acute ischemic stroke (AIS) is the primary type of stroke (accounting for ~70% of all stroke cases), which is characterized by immune system disorder, severe neurological deficits, etc. (5–10). Gradually, diversified therapeutic strategies (including thrombolysis, antiplatelet treatment, anticoagulants, and neuroprotective agents) have been introduced in an attempt to eliminate arterial occlusion, restore blood flow to the brain, and improve the recovery of neurological function; however, AIS is disease prone to recurrence, which requires continuous attention (11–16). Therefore, it is imperative to develop objective biomarkers to help identify patients with AIS as soon as possible, predict their outcomes, and then adjust the treatment regimens accordingly.

Cell division cycle 42 (CDC42), a small hydrolase of guanosine triphosphate (GTPase), acts as a signal transduction convergence point that mediates many signaling pathways. Moreover, it is reported that CDC42 regulates blood lipids, blood vessel development, CD4⁺ T-cell differentiation, microglial process, and neuronal apoptosis in some cardiovascular and cerebrovascular diseases (including ischemic brain injury, coronary heart disease, and cerebrovascular malformations) (17–23). For instance, a study found that CDC42 can act as an upstream activator of the c-Jun N-terminal kinase (JNK) signaling pathway to govern neuronal apoptosis in ischemic brain injury (19). Another study explored the correlation between CDC42 and T helper (Th) 2 cells, Th17 cells, and blood lipids in patients with coronary heart disease (20). Interestingly, these CDC42-modulated biological processes (mentioned above) behave as underlying pathogenesis of AIS, implying that CDC42 might be implicated in the development of AIS (6, 8, 24). Additionally, an in vitro study reported that the activation of CDC42 promoted the migration of endogenous neural stem/progenitors cells after ischemic stroke, which facilitates the recovery of injured brain tissue (25). However, the detailed clinical role of CDC42 in patients with AIS remains unanswered.

In this study, the expression of CDC42 was detected in patients with AIS during a 3-year follow-up period with the aim of evaluating the longitudinal changes of CDC42 and its correlation with disease severity, Th1/2/17 cells, and the prognosis in patients with AIS.