The Peptide AF-16 and the AF Protein Counteract Intracranial Hypertension
Intracranial hypertension develops after, for example, trauma, stroke and brain inflammation, and contributes to increased morbidity, mortality, and persistent neuropsychiatric sequelae. Nonsurgical therapy offers limited relief. We investigated whether t
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Abstract Intracranial hypertension develops after, for example, trauma, stroke and brain inflammation, and contributes to increased morbidity, mortality, and persistent neuropsychiatric sequelae. Nonsurgical therapy offers limited relief. We investigated whether the peptide AF-16 and the endogenous protein Antisecretory Factor (AF) counteracted abnormal fluid transfer by cells, and lowered raised intracranial pressure (ICP). Adult rats, infected with an encephalitogenic Herpes simplex virus (HSV-1), developed after 5 days’ sickness of increasing severity. AF-16 rescued all rats while vehicle treatment only saved 20%. AF-16 from day 4 reduced the ICP in HSV-1infected rats from 30.7 to 14.6 mmHg and all survived without sequelae. A standardised closed head brain injury in rats raised the ICP. Continuous and intermittent AF-16 kept ICP at an almost normal level. A single dose of AF-16 maintained the raised ICP after a TBI lowered during 3–9 h. The AF protein, enriched in egg yolk, similarly lowered the post-traumatically raised ICP in rats. AF-16 also lowered the ICP in rabbits with diffuse brain injury. We conclude that the peptide AF-16 and the AF protein offer new approaches to treat raised ICP with no side effects. Keywords Raised intracranial pressure • Herpes simplex virus encephalitis • Neurotrauma • Sagittal rotational acceleration head and neck impulse • Head injury management • Traumatic brain injury • Brain herniation • Antisecretory factor • S5a
H.-A. Hansson (), E. Jennische, and S. Lange Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, P.O. Box 440, SE 40530 Göteborg, Sweden e-mail: [email protected] M. Al-Olama Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, P.O. Box 440, SE 40530 Göteborg, Sweden and Department of Neurosurgery, Sahlgren’s University Hospital, SE-41345 Göteborg, Sweden K. Gatzinsky Department of Neurosurgery, Sahlgren’s University Hospital, SE-41345 Göteborg, Sweden
Introduction Raised intracranial pressure (ICP) commonly evolves after a head trauma, stroke, blast, intracranial haemorrhage, brain tumour, inflammation or infection [2, 5, 16]. Intracranial hypertension disturbs the blood circulation and hampers the exchange of nutrients, oxygen and metabolites. The turnover of cerebrospinal fluid (CSF) is impaired and the brain parenchyma is concomitantly mechanically distorted and even dislocated by the elevated ICP, especially if pressure gradients develop. The ICP reflects the balance between the close to fixed craniospinal volume and its ability to accommodate additionally added volume to the incompressible content. Swelling of the brain owing to cytotoxic oedema prevails at intracellular fluid accumulation, most evidently in astrocytes [2, 5, 12, 15, 16]. Leakage from blood vessels, i.e. vasogenic or extracellular oedema, and haemorrhage, increases preferentially the extracellular fluid volume. The volumes of brain parenchyma, blood and CSF may vary dynamically. The cytotoxic and the vasogenic mechanisms are concomita
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