Evidence map›Paper›PMID 40598588›Full record

ArticleJournal of nanobiotechnology2025

Brain targeted lipid nanoparticles with Hv1 inhibitors alleviate neuroinflammation post-ischemic stroke.

Zeyu Yang, Lei Jin, Longxiang Li, Yu Wu, Wenchao Liu, Xin Feng, Liyan Li, Fa Jin, Yiming Bi, Ran Li and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of nanobiotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Fluctuating hydrogen-bond network of the Hv1 ion channel.Computational and structural biotechnology journal · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Zeyu Yang *Neurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China.
Lei Jin *Neurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China.
Longxiang Li *Neurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China.
Yu WuNeurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China.
Wenchao LiuNeurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China.
Xin FengNeurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China.
Liyan LiSchool of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou, 510275, China.
Fa JinNeurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China.
Yiming BiNeurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China.
Ran LiNeurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China.
Shenquan GuoNeurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China.
Yanan WangThe Second Affiliated Hospital of Guangzhou, University of Chinese Medicine, Guangzhou, 510000, China.
Boyang WeiNeurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China. zjyywby@126.com.
Yanchao LiuNeurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China. liuyanchao_zj@126.com.
Xifeng LiNeurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China. nflxf@126.com.
Chuanzhi DuanNeurosurgery Center, Department of Cerebrovascular Surgery, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, The National Key Clinical Specialty, Southern Medical University, Guangzhou, 510282, China. doctor_duanzj@163.com.

Funding

Guangzhou Science and Technology Project SL2022A04J00214National Health and Family Planning Commission of the People's Republic of China GWJJQ2022100104National Natural Science Foundation of China 82001300National Natural Science Foundation of China 82271297
6 · The paper itself

Abstract

backgroundIschemic stroke (IS) represents a significant global health burden. Current therapeutic options face problems such as window narrowing and reperfusion injury risk. Moreover, with increasing aging and risk factors, novel treatment strategies are urgently needed. NADPH oxidase (NOX)-mediated oxidative stress in microglia is a critical mechanism driving neuroinflammation and cell death. Hv1, a voltage-gated proton channel highly expressed in microglia, synergizes with NOX to generate reactive oxygen species (ROS), exacerbating brain damage. YHV984, a potent Hv1 inhibitor, alleviates post-IS neuroinflammation but faces clinical limitations due to potential toxic side effects and solubility issues. To improve the physicochemical and pharmacokinetic properties of YHV984 for specific Hv1 inhibition in the brain, the multifunctional nanoparticles consisting of a T7-targeting peptide and lipid nanoparticles (LNP) were developed to deliver YHV984 (T7-LNP@YHV984).

resultsThe results demonstrated that T7-LNP@YHV984 exhibited good stability and brain targeting capability, effectively crossing the blood-brain barrier (BBB) and accumulating within microglia. This targeted delivery significantly suppressed Hv1 expression and activation of the NLRP3 inflammasome pathway in the damaged brain. Furthermore, it promoted the polarization of microglia towards the M2 phenotype, enhancing the release of anti-inflammatory factors, alleviating neuroinflammation and improved neuronal survival. Additionally, T7-LNP@YHV984 improved survival and facilitated neurological recovery in post-IS mice.

conclusionsT7-LNP@YHV984 multifunctional nanoparticles with long-term stability emerged as a potent strategy to alleviate reperfusion injury and inhibit neuroinflammation post-IS. By precisely targeting Hv1 in microglia, the nanoparticles effectively suppressed microglia-induced neuroinflammation, minimizing off-target effects. This innovation offers novel insights into stroke treatment and neuroprotective strategies.

Indexed as

BrainIschemic StrokeNanoparticlesNeuroinflammatory DiseasesAnimalsBlood-Brain BarrierIon ChannelsLipidsLiposomesMaleMiceMice, Inbred C57BLMicrogliaNLR Family, Pyrin Domain-Containing 3 ProteinHv1 proton channel, mouseIon ChannelsLipid NanoparticlesLipidsLiposomesNLR Family, Pyrin Domain-Containing 3 ProteinBrain-targeted LNPIschemic strokeMicroglialNeuroinflammationVoltage-gated proton channel Hv1

Identifiers

PMID40598588
PMCPMC12211482

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.