2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
July 17th, 2025
Version: 2
University of Birmingham
neuroscience
biorxiv

Adult organotypic brain slice cultures recapitulate extracellular matrix remodelling in haemorrhagic stroke

Hewitt, B. J.Open in Google Scholar•Roberts, L.Open in Google Scholar•Roberts, J. A.Open in Google Scholar•Fulton, D.Open in Google Scholar•Hill, L.Open in Google Scholar•Kitchen, P.Open in Google Scholar•Bill, R. M.Open in Google Scholar•Botfield, H.Open in Google Scholar

Haemorrhagic stroke is a devastating condition characterised by vessel rupture and free blood within the brain parenchyma or cerebrospinal fluid (CSF) filled spaces. Across the major subtypes of haemorrhagic stroke (subarachnoid, intracerebral, and intraventricular haemorrhages), the presence of blood in the CSF generates significant tissue damage in the first 72 hours after the event, known as early brain injury (EBI). EBI includes neuroinflammation, blood-brain barrier breakdown and dysregulation of extracellular matrix (ECM) dynamics. ECM dysfunction has been shown to trigger fibrosis of the cortical blood vessels, limiting normal CSF circulation and resulting in the buildup of metabolic waste or the development of post-haemorrhagic hydrocephalus. Limiting or preventing this fibrosis may therefore reduce the rate of morbidity experienced by survivors, providing a potential avenue for non-surgical treatment to reduce secondary brain injury post-stroke. Despite this, current in vivo approaches fail to differentiate between the effect of blood products and secondary consequences including intracranial pressure (ICP) elevation and mass effect. Here, we describe an adult rat organotypic brain slice culture (OBSC) model of haemorrhagic stroke which enables the identification of the effect of blood products on ECM dysregulation. We demonstrate the distribution of key cell types across a time course of 0, 3 and 7 days in culture, indicating that such cultures are viable for a minimum of 7 days. Using immunofluorescence staining, Western blotting and RNA sequencing, we show that exposure of OBSCs to lysed blood markedly increases ECM deposition around cortical blood vessels. This is accompanied by dysregulation of ECM regulatory genes and upregulation of inflammation and oxidative stress-related genes, successfully recapitulating the changes seen in human stroke survivors. This versatile ex vivo model provides a translational platform to further understanding of haemorrhagic stroke pathophysiology and develop or trial novel therapeutics prior to progression to in vivo stroke studies.

Similar Papers

biorxiv
Fri Jul 18 2025
Transcriptomic analysis reveals new reparative mechanisms of SCF and GCSF - reduced neuropathology in aged APPPS1 mice
Alzheimers Disease, AD, is a neurodegenerative disease characterized by amyloid plaque deposition, tau hyperphosphorylation, neuroinflammation, and cognitive decline. Our previous studies showed that combined treatment with stem cell factor, SCF, and granulocyte colony stimulating factor, GCSF, reduces AD pathology in APPPS1 mice. This study aimed to explore the molecular mechanism underlying SCF ...
Addo, A.
•
Li, B.
•
Murikinati, S.
•
Gardner, R.
•
Zhao, L.-R.
biorxiv
Fri Jul 18 2025
The relationship between sleep and cognitive performance on tests of pattern separation
Study objectives: Sleep disturbances are considered both a risk factor and symptom of dementia. The present research aimed to identify cognitive tests in which performance is associated with objective sleep quality or quantity, focusing on cognitive tests designed to evaluate the earliest cognitive changes in dementia. Methods: We recruited younger and older adults and remotely monitored their sle...
Roenningen, A. E.
•
Gill, D.
•
Kent, B. A.
biorxiv
Thu Jul 17 2025
Developmental Stage-Dependent Transcriptomic Responses to Neonatal Intraventricular Hemorrhage
Neonatal intraventricular hemorrhage (IVH) is a major complication of preterm birth, yet how developmental stage influences the brains response to injury remains unclear. We performed single-nucleus RNA sequencing on rat brains 24 hours after IVH at postnatal day 2 (PND2) or day 5 (PND5) to define transcriptional responses across cell types. We identified 42 distinct cell populations and found tha...
Wallace-Anthony, E.
•
Zamorano, M.
•
Vekaria, H. J.
•
Oldham, B. B.
...•
Miller, B. A.
biorxiv
Thu Jul 17 2025
Investigating the Effects of Synbiotic Intervention on Working Memory, Attention, and Inhibitory Control in Healthy Young Women
The gut-brain axis plays a key role in the bidirectional communication between the gastrointestinal system and the brain, with gut microbiota significantly influencing cognitive function. While synbiotic and probiotic interventions have shown potential cognitive benefits, results across studies remain mixed. This randomized, controlled, repeated-measures study investigated the effects of a 15-day ...
Salimi, Y.
•
Namdarzadeh, B.
•
Dehghani-Arani, F.
•
Vahabie, A.-H.
•
Rezayat, E.
biorxiv
Thu Jul 17 2025
Variants in glycine decarboxylase activate mechanisms of mitochondrial energy metabolism in the brain.
Brain energy metabolism is produced from glucose by mitochondrial oxidative phosphorylation. Variants in the mitochondrial enzyme glycine decarboxylase (GLDC) cause a rare neurological disease, non-ketotic hyperglycinemia (NKH), with expected hallmarks of brain glycine elevation and responsiveness to folate deficiency that are equivalent to the severity of Gldc mutations. We remarkably find that b...
Haldar, K.
•
Lopez-Ramirez, A.
•
Worth, A.
•
Wang, Z.
...•
Padmanabhan, P.
biorxiv
Thu Jul 17 2025
Bmal1 expression is minimal or absent in human and mouse cerebral microglia
Microglia orchestrate immunological responses in the brain and play an important role in maintaining homeostatic brain functions. Several studies have reported clock gene expression in microglia and the circadian rhythm they drive has been linked to the modulation of immune responses and neuronal functions. In the current study, complementary approaches, including immunofluorescence, multiplexed f...
Rahimian, R.
•
Simard, S.
•
Chawla, A.
•
Zhu, L.
...•
Mechawar, N.
biorxiv
Thu Jul 17 2025
Motor learning drives region-specific transcriptomic remodeling in the motor cortex and dorsal striatum
Motor learning depends on coordinated activity across the motor cortex (M1) and dorsal striatum (dSTR), yet the molecular mechanisms driving learning-related synaptic and circuit remodeling remain unclear. Here, we combine activity-dependent genetic labeling (TRAP) with single-cell RNA sequencing to generate an unbiased, cell type-resolved transcriptional atlas of behaviorally engaged populations ...
Sun, Y.
•
Roth, R. H.
•
Hwang, F.-J.
•
Wang, S.
•
Ding, J. B.
biorxiv
Thu Jul 17 2025
Neuroligin-3 interaction with CSPG4 regulates normal and malignant glial precursors through PIEZO1
Glioma pathophysiology is robustly regulated by interactions with neurons. Key to these interactions is the role of neuroligin-3 (NLGN3), a synaptic adhesion molecule shed in response to neuronal activity1-5 that functions as a paracrine factor crucial for glioma growth. Here, we elucidate the mechanistic pathway whereby shed NLGN3 interacts with glioma and their normal glial counterpart. NLGN3 in...
Gillespie, S. M.
•
Kim, Y. S.
•
Geraghty, A. C.
•
Yalcin, B.
...•
Monje, M.
biorxiv
Thu Jul 17 2025
Diet context gates AgRP neuron involvement in Semaglutide-induced weight loss
Semaglutide, a GLP-1R agonist, is widely used for obesity and type 2 diabetes, but its neural mechanisms remain unclear. AgRP neurons regulate energy balance, yet their role in the effects of Semaglutide is unknown. We show that sustained treatment of female mice with Semaglutide leads to activation rather than inhibition of AgRP neurons. Ablation or hypofunction of AgRP neurons through cell-speci...
d'Avila, M.
•
Collado-Perez, R.
•
Liu, Z.
•
Horvath, T.
biorxiv
Thu Jul 17 2025
Bounds on the computational complexity of neurons due to dendritic morphology
The simple linear threshold units used in many artificial neural networks have a limited computational capacity. Famously, a single unit cannot handle non-linearly separable problems like XOR. In contrast, real neurons exhibit complex morphologies as well as active dendritic integration, suggesting that their computational capacities outperform those of simple linear units. Considering specific fa...
Agrawal, A.
•
Buice, M. A.