RAB7L1 Participates in Secondary Brain Injury Induced by Experimental Intracerebral Hemorrhage in Rats

J Mol Neurosci. 2021 Jan;71(1):9-18. doi: 10.1007/s12031-020-01619-3. Epub 2020 Jul 20.


RAB7, a member of RAS oncogene family-like 1 (RAB7L1), is a GTPase belonging to the Rab family and acts as an upstream regulator to regulate the kinase activity of leucine-rich repeat kinase 2 (LRRK2). Although LRRK2 has been shown to aggravate secondary brain injury (SBI) after intracerebral hemorrhage (ICH), it is unknown whether RAB7L1 is also involved in this process. The purpose of the present study was to investigate the role of RAB7L1 in ICH-induced SBI in vivo. Autologous blood was injected into adult male Sprague-Dawley rats to induce an ICH model in vivo. The results showed that the protein levels of RAB7L1 increased after ICH. Overexpression of RAB7L1 induced neuronal apoptosis and damage, as demonstrated by TUNEL-positive and FJB-positive cells, and exacerbated ICH-induced learning and cognitive dysfunctions; in contrast, downregulation of RAB7L1 via RNA interference yielded comparatively opposite changes in these parameters. In summary, this study demonstrates that RAB7L1 promotes SBI after ICH and may represent a potential target for ICH therapy.

Keywords: Apoptosis; Intracerebral hemorrhage; Rab7L1; Secondary brain injury.

MeSH terms

  • Animals
  • Apoptosis
  • Basal Ganglia
  • Blood
  • Brain Damage, Chronic / etiology*
  • Brain Damage, Chronic / genetics
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / genetics*
  • Cognition Disorders / etiology
  • Cognition Disorders / genetics
  • Disease Models, Animal
  • Gene Expression Regulation
  • Injections
  • Injections, Intraventricular
  • Learning Disabilities / etiology
  • Learning Disabilities / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism
  • Male
  • Morris Water Maze Test
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / genetics
  • Neurons / pathology
  • Phosphorylation
  • Protein Processing, Post-Translational
  • RNA, Small Interfering / administration & dosage
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Stereotaxic Techniques
  • Up-Regulation
  • rab GTP-Binding Proteins / antagonists & inhibitors
  • rab GTP-Binding Proteins / biosynthesis
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / physiology*


  • Nerve Tissue Proteins
  • RNA, Small Interfering
  • LRRK2 protein, rat
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Rab29 protein, rat
  • rab GTP-Binding Proteins