Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS
| Autor: | Jiyan An, Natasha L. Grimsey, Sarah Waters, Birger Dieriks, Mike Dragunow, Clinton Turner, Robert Bowser, Maurice A. Curtis, Henry J. Waldvogel, Richard L.M. Faull, Helen C. Murray, Yibin Zhang, Molly E. V. Swanson, Emma L. Scotter |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Cord TDP-43 Lower motor neuron Pathology and Forensic Medicine Blood–brain barrier White matter 03 medical and health sciences Hemoglobins Cellular and Molecular Neuroscience 0302 clinical medicine Cerebrospinal fluid Lumbar medicine Humans Hemoglobin Amyotrophic lateral sclerosis Blood-spinal cord barrier RC346-429 Aged Aged 80 and over Motor Neurons Cerebrospinal Fluid Leak business.industry Research Amyotrophic Lateral Sclerosis Middle Aged Motor neuron Spinal cord medicine.disease 030104 developmental biology medicine.anatomical_structure Spinal Cord Blood-Brain Barrier Female Neurology. Diseases of the nervous system Neurology (clinical) ALS business 030217 neurology & neurosurgery Human |
| Zdroj: | Acta Neuropathologica Communications, Vol 9, Iss 1, Pp 1-17 (2021) Acta Neuropathologica Communications |
| ISSN: | 2051-5960 |
| DOI: | 10.1186/s40478-021-01244-0 |
| Popis: | BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving progressive degeneration of upper and lower motor neurons. Both lower motor neuron loss and the deposition of phosphorylated TDP-43 inclusions display regional patterning along the spinal cord. The blood-spinal cord barrier (BSCB) ordinarily restricts entry into the spinal cord parenchyma of blood components that are neurotoxic, but in ALS there is evidence for barrier breakdown. Here we sought to examine whether BSCB breakdown, motor neuron loss, and TDP-43 proteinopathy display the same regional patterning across and along the spinal cord.MethodsWe measured cerebrospinal fluid (CSF) hemoglobin in living ALS patients (n=87 controls, n=236 ALS) as a potential biomarker of BSCB and blood-brain barrier leakage. We then immunostained cervical, thoracic, and lumbar post mortem spinal cord tissue (n=5 controls, n=13 ALS) and employed semi-automated imaging and analysis to quantify and map lower motor neuron loss and phosphorylated TDP-43 inclusion load against hemoglobin leakage.ResultsMotor neuron loss and TDP-43 proteinopathy were seen at all three levels of the ALS spinal cord, with most abundant TDP-43 deposition in the ventral grey (lamina IX) of the cervical and lumbar cord. In contrast, hemoglobin leakage was observed along the ALS spinal cord axis but was most severe in the dorsal grey and white matter in the thoracic spinal cord.ConclusionsOur data show that leakage of the blood-spinal cord barrier occurs during life but at end-stage its distribution is independent from the major motor neuron pathology and is unlikely to be a major contributor to pathogenesis in ALS. |
| Databáze: | OpenAIRE |
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