Format

Send to

Choose Destination
Neurologia. 2018 May;33(4):211-223. doi: 10.1016/j.nrl.2016.07.002. Epub 2016 Aug 25.

Histological changes in the rat brain and spinal cord following prolonged intracerebroventricular infusion of cerebrospinal fluid from amyotrophic lateral sclerosis patients are similar to those caused by the disease.

[Article in English, Spanish]

Author information

1
Laboratorio de Neurobiología, Instituto de Neurociencias, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, España. Electronic address: ulisesalfonso.gomez@salud.madrid.org.
2
Servicio de Neurología, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, España.
3
Servicio de Neurocirugía, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, España.
4
Laboratorio de Neurobiología, Instituto de Neurociencias, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, España.
5
Laboratorio de Neurobiología, Instituto de Neurociencias, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, España; Servicio de Neurología, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, España.
6
Instituto Teófilo Hernando, Departamento de Farmacología Terapéutica, Universidad Autónoma de Madrid, Madrid, España.

Abstract

INTRODUCTION:

Cerebrospinal fluid (CSF) from amyotrophic lateral sclerosis (ALS) patients induces cytotoxic effects in in vitro cultured motor neurons.

MATERIAL AND METHODS:

We selected CSF with previously reported cytotoxic effects from 32 ALS patients. Twenty-eight adult male rats were intracerebroventricularly implanted with osmotic mini-pumps and divided into 3 groups: 9 rats injected with CSF from non-ALS patients, 15 rats injected with cytotoxic ALS-CSF, and 4 rats injected with a physiological saline solution. CSF was intracerebroventricularly and continuously infused for periods of 20 or 43days after implantation. We conducted clinical assessments and electromyographic examinations, and histological analyses were conducted in rats euthanised 20, 45, and 82days after surgery.

RESULTS:

Immunohistochemical studies revealed tissue damage with similar characteristics to those found in the sporadic forms of ALS, such as overexpression of cystatinC, transferrin, and TDP-43 protein in the cytoplasm. The earliest changes observed seemed to play a protective role due to the overexpression of peripherin, AKTpan, AKTphospho, and metallothioneins; this expression had diminished by the time we analysed rats euthanised on day 82, when an increase in apoptosis was observed. The first cellular changes identified were activated microglia followed by astrogliosis and overexpression of GFAP and S100B proteins.

CONCLUSION:

Our data suggest that ALS could spread through CSF and that intracerebroventricular administration of cytotoxic ALS-CSF provokes changes similar to those found in sporadic forms of the disease.

KEYWORDS:

ALS experimental model; Amyotrophic lateral sclerosis; Citotoxicidad; Cytotoxicity; Enfermedades neurodegenerativas; Esclerosis lateral amiotrófica; Modelo experimental ELA; Neurodegenerative diseases; Periferina; Peripherin; TDP-43

PMID:
27570180
DOI:
10.1016/j.nrl.2016.07.002
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Ediciones Doyma, S.L.
Loading ...
Support Center