The peptide AF-16 abolishes sickness and death at experimental encephalitis by reducing increase of intracranial pressure.

• Elevated intracranial pressure (ICP) is strongly aggravating the injury at brain inflammation, resulting in persistent neurological and psychiatric malfunctions. There is no efficient pharmacological treatment to achieve beneficial ICP reduction. Here, the peptide AF-16, comprising the amino terminal part of the endogenous protein Antisecretory Factor (AF), was used to suppress the raised ICP in experimental herpes simplex encephalitis (HSE) in rats. Intranasal instillation of the peptide AF-16 counteracted the ICP elevation and the prevalence of ICP spikes, abrogated the neurological morbidity, and abolished the mortality in a dose-dependent manner. AF-16, 25 microg twice daily intranasally, rescued all animals with HSE and abrogated neurological malfunction. In contrast, only 10% of the rats survived if treated with the vehicle. A single intranasal dose of 25 microg AF-16 to a rat displaying overt HSE symptoms reduced the ICP to normal levels within an hour. No effects on viral replication or antigen distribution were demonstrable. Thus, AF-16 abolished the prevalence of sickness signs, ICP elevation, neurological malfunctions and completely prevented deaths. We advocate use of AF-16 for suppression of elevated ICP.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Administration

Intranasal

Animals

Antidiarrheals

administration & dosage

therapeutic use

Brain

drug effects

pathology

physiopathology

Cells

Cultured

Dose-Response Relationship

Drug

Encephalitis

Herpes Simplex

drug therapy

physiopathology

virology

Herpesvirus 1

Human

genetics

metabolism

Humans

Immunohistochemistry

Intracranial Hypertension

drug therapy

physiopathology

Intracranial Pressure

drug effects

physiology

Male

Neurons

drug effects

pathology

virology

Neuropeptides

administration & dosage

therapeutic use

Peptides

administration & dosage

therapeutic use

Polymerase Chain Reaction

Rats

Rats

Sprague-Dawley

Treatment Outcome

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)