Metformin reduces neuronal damage and promotes neuroblast proliferation and differentiation in a cerebral ischemia/reperfusion rat model

Yuan, Rui; Wang, Yu; Li, Qingyun; Zhen, Fei; Li, Xinyu; Lai, Qingwei; Hu, Peng; Wang, Xiao; Zhu, Yansha; Fan, Huiying; Yao, Ruiqin

doi:10.1097/wnr.0000000000001190

Cited by 27 publications

(9 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We immediately performed a literature search. Instead of finding metformin caused neuroinflammation, the search returned 4 animal articles indicating metformin reduces brain damage due to ischemia, decreases NPP, has anti-neuroinflammation properties, and promotes NSC activation [969][970][971][972]. The very anxious PPI member agreed to a one month trial.…”

Section: Plos Onementioning

confidence: 99%

The leptomeninges as a critical organ for normal CNS development and function: First patient and public involved systematic review of arachnoiditis (chronic meningitis)

Palackdkharry¹,

Wottrich²,

Dienes³

et al. 2022

PLoS ONE

View full text Add to dashboard Cite

Background & importance This patient and public-involved systematic review originally focused on arachnoiditis, a supposedly rare “iatrogenic chronic meningitis” causing permanent neurologic damage and intractable pain. We sought to prove disease existence, causation, symptoms, and inform future directions. After 63 terms for the same pathology were found, the study was renamed Diseases of the Leptomeninges (DLMs). We present results that nullify traditional clinical thinking about DLMs, answer study questions, and create a unified path forward. Methods The prospective PRISMA protocol is published at Arcsology.org. We used four platforms, 10 sources, extraction software, and critical review with ≥2 researchers at each phase. All human sources to 12/6/2020 were eligible for qualitative synthesis utilizing R. Weekly updates since cutoff strengthen conclusions. Results Included were 887/14286 sources containing 12721 DLMs patients. Pathology involves the subarachnoid space (SAS) and pia. DLMs occurred in all countries as a contributor to the top 10 causes of disability-adjusted life years lost, with communicable diseases (CDs) predominating. In the USA, the ratio of CDs to iatrogenic causes is 2.4:1, contradicting arachnoiditis literature. Spinal fusion surgery comprised 54.7% of the iatrogenic category, with rhBMP-2 resulting in 2.4x more DLMs than no use (p<0.0001). Spinal injections and neuraxial anesthesia procedures cause 1.1%, and 0.2% permanent DLMs, respectively. Syringomyelia, hydrocephalus, and arachnoid cysts are complications caused by blocked CSF flow. CNS neuron death occurs due to insufficient arterial supply from compromised vasculature and nerves traversing the SAS. Contrast MRI is currently the diagnostic test of choice. Lack of radiologist recognition is problematic. Discussion & conclusion DLMs are common. The LM clinically functions as an organ with critical CNS-sustaining roles involving the SAS-pia structure, enclosed cells, lymphatics, and biologic pathways. Cases involve all specialties. Causes are numerous, symptoms predictable, and outcomes dependent on time to treatment and extent of residual SAS damage. An international disease classification and possible treatment trials are proposed.

show abstract

Section: Plos Onementioning

confidence: 99%

The leptomeninges as a critical organ for normal CNS development and function: First patient and public involved systematic review of arachnoiditis (chronic meningitis)

Palackdkharry¹,

Wottrich²,

Dienes³

et al. 2022

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…[ 23 ] We, along with others, have found that metformin fosters mitochondrial biogenesis and bolsters mitochondrial activity and function. [ 26 , 28 , 29 , 30 ] Thus, we asked if metformin could mitigate the phenotype and molecular profile of the POLG‐organoid. We exposed patient cortical organoids to 250 µ m metformin from day 6 and observed an enhancement in cortical organoid structure and morphology after a 30‐day (Figure 7A ).…”

Section: Resultsmentioning

confidence: 99%

Hallmark Molecular and Pathological Features of POLG Disease are Recapitulated in Cerebral Organoids

Chen,

Yangzom,

Hong

et al. 2024

Advanced Science

View full text Add to dashboard Cite

In this research, a 3D brain organoid model is developed to study POLG‐related encephalopathy, a mitochondrial disease stemming from POLG mutations. Induced pluripotent stem cells (iPSCs) derived from patients with these mutations is utilized to generate cortical organoids, which exhibited typical features of the diseases with POLG mutations, such as altered morphology, neuronal loss, and mitochondiral DNA (mtDNA) depletion. Significant dysregulation is also identified in pathways crucial for neuronal development and function, alongside upregulated NOTCH and JAK‐STAT signaling pathways. Metformin treatment ameliorated many of these abnormalities, except for the persistent affliction of inhibitory dopamine‐glutamate (DA GLU) neurons. This novel model effectively mirrors both the molecular and pathological attributes of diseases with POLG mutations, providing a valuable tool for mechanistic understanding and therapeutic screening for POLG‐related disorders and other conditions characterized by compromised neuronal mtDNA maintenance and complex I deficiency.

show abstract

“…Also, in acute stroke patients with type 2 diabetes, metformin could improve the neurological function and oxidative stress status by the AMPK/mTOR signaling pathway and oxidative stress [ 51 ], and in acute ischemic injury, prestroke metformin treatment was neuroprotective involving AMPK reduction [ 52 ]. Metformin was a favorable target in therapeutic intervention of cerebral ischemia injury models [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Prestroke Metformin Use on the 1‐Year Prognosis of Intracerebral Hemorrhage Patients with Type 2 Diabetes

Zeng

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Background. Although recent studies have focused on the use of metformin in treating ischemic stroke, there is little literature to support whether it can treat intracerebral hemorrhage (ICH). Therefore, this study is aimed at evaluating the possible effects of prestroke metformin (MET) on ICH patients with type 2 diabetes. Methods. From January 2010 to December 2019, all first-ever ICH patients with type 2 diabetes from our hospitals were included. All discharged patients would receive a one-time follow-up at 1 year after admission. Death, disability, and recurrence events were recorded. Results. We included 730 patients for analysis (the median age: 65 [IQR, 56-72] years and 57.7% was men). Of those patients, 281 (38.5%) had received MET before ICH (MET+), whereas 449 (61.5%) had not (MET−). MET (+) patients had a lower median baseline hematoma volume than did MET (-) patients (9.6 ml [IQR, 5.3-22.4 ml] vs. 14.7 ml [IQR, 7.9-28.6 ml]; P < 0.001 ). The inhospital mortality events were not significantly reduced in the MET (+) group compared with the MET (-) group (6.4% vs 8.9%, respectively; absolute difference, −2.5% [95% CI, −3.9% to −0.7%]; OR, 0.70 [95% CI, 0.39 to 1.27]; P = 0.22 ). The 1-year mortality events were not significantly reduced in the MET (+) group compared with the MET (-) group (14.1% vs 17.4%, respectively; absolute difference, −3.3% [95% CI, −5.1% to −1.8%]; OR, 0.73 [95% CI, 0.47 to 1.14]; P = 0.16 ). The 1-year disability events were not significantly reduced in the MET (+) group compared with the MET (-) group (28.4% vs 34.1%, respectively; absolute difference, −5.7% [95% CI, −8.2% to −3.3%]; OR, 0.77 [95% CI, 0.52 to 1.13]; P = 0.18 ). Finally, the recurrence rates in those two groups were not significantly different (MET [+] vs. MET [-]: 6.4% vs. 5.9%; absolute difference, 0.5% [95% CI, 0.2% to 1.3%]; OR, 1.08 [95% CI, 0.51 to 2.28]; P = 0.84 ). Conclusions. Pre-ICH metformin use was not associated with inhospital mortality and 1-year prognosis in diabetic ICH patients.

show abstract

Metformin reduces neuronal damage and promotes neuroblast proliferation and differentiation in a cerebral ischemia/reperfusion rat model

Cited by 27 publications

References 23 publications

The leptomeninges as a critical organ for normal CNS development and function: First patient and public involved systematic review of arachnoiditis (chronic meningitis)

The leptomeninges as a critical organ for normal CNS development and function: First patient and public involved systematic review of arachnoiditis (chronic meningitis)

Hallmark Molecular and Pathological Features of POLG Disease are Recapitulated in Cerebral Organoids

Prestroke Metformin Use on the 1‐Year Prognosis of Intracerebral Hemorrhage Patients with Type 2 Diabetes

Contact Info

Product

Resources

About