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-1-infected 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.
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Acknowledgements
The authors are grateful to Svante Höjer, Samba Sensors AB, for advice and support, Dr. Hong Zhu and Ms. Iris Gustafsson, Histocenter AB, for performing the immunohistochemistry, and Ms I. Jonson and Ms. M. Rosenkvist for invaluable technical help and support. Supported by grants from the Swedish Government under the LUA/ALF agreement (grant # 71570), Sahlgren’s University Hospital (grant # 83030), the Ministry of High Education UAE, JK Jubileumsfond, Magnus Bergvall Foundation, W. and M. Lundgren Foundation, Frimurare-Barnhus direktionen, Göteborg Medical Society, AB Nectin, and Lantmännen AS-Faktor AB.
Conflict of interest statement
E. Jennische, S. Lange and H.-A. Hansson declare potential financial conflict of interest because of patents and patent applications. M. Al-Olama and K. Gatzinsky have no financial conflict of interest.
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Hansson, HA., Al-Olama, M., Jennische, E., Gatzinsky, K., Lange, S. (2012). The Peptide AF-16 and the AF Protein Counteract Intracranial Hypertension. In: Schuhmann, M., Czosnyka, M. (eds) Intracranial Pressure and Brain Monitoring XIV. Acta Neurochirurgica Supplementum, vol 114. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0956-4_73
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DOI: https://doi.org/10.1007/978-3-7091-0956-4_73
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