Effect of caffeine on cerebral blood flow response to somatosensory stimulation

• Published in: Journal of cerebral blood flow and metabolism Vol. 25; no. 6; pp. 775 - 784
• Main Authors: Meno, Joseph R., Nguyen, Thien-son K., Jensen, Elise M., Alexander West, G., Groysman, Leonid, Kung, David K., Ngai, Al C., Britz, Gavin W., Winn, H. Richard
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.06.2005; Lippincott Williams & Wilkins; Sage Publications Ltd
• Subjects: Adenosine - pharmacology; Animals; Biological and medical sciences; Caffeine - cerebrospinal fluid; Caffeine - pharmacology; Central Nervous System Stimulants - cerebrospinal fluid; Central Nervous System Stimulants - pharmacology; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cerebrovascular Circulation - drug effects; Electric Stimulation; Fundamental and applied biological sciences. Psychology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Injections, Intravenous; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Physical Stimulation; Pia Mater - blood supply; Rats; Rats, Sprague-Dawley; Sciatic Nerve - physiology; Somatosensory Cortex - blood supply; Somatosensory Cortex - physiology; Theophylline - pharmacology; Vascular diseases and vascular malformations of the nervous system; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Vertebrates: nervous system and sense organs; caffeine; theophylline; cerebral circulation; neuronal activity; Nervous system diseases; CNS stimulant; Psychotropic; Bronchodilator; Antiasthma agent; Cerebral disorder; Blood flow; Respiratory analeptic; Central nervous system disease; Xanthine derivatives; Cerebrovascular disease; Theophylline; Caffeine
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/sj.jcbfm.9600075

Despite caffeine's wide consumption and well-documented psychoactive effects, little is known regarding the effects of caffeine on neurovascular coupling. In the present study, we evaluated the effects of caffeine, an adenosine receptor antagonist, on intracerebral arterioles in vitro and subsequently, on the pial circulation in vivo during cortical activation induced by contralateral sciatic nerve stimulation (SNS). In our in vitro studies, we utilized isolated intracerebral arterioles to determine the effects of caffeine (10 or 50 μmol/L) on adenosine-induced vasodilatation. At the lower concentration, caffeine was without effect, but at the higher concentration, caffeine produced significant attenuation. In our in vivo studies, we determined the cerebrospinal fluid (CSF) caffeine concentrations at 15, 30, and 60 mins after intravenous administration of 5, 10 and 40 mg/kg. At the latter two concentrations, CSF levels exceeded 10 μmol/L. We then evaluated the pial arteriolar response during cortical activation caused by contralateral SNS after administering caffeine intravenously (0, 5, 10, 20 30, and 40 mg/kg). The pial circulation was observed through a closed cranial window in chloralose-anesthetized Sprague—Dawley rats. The contralateral sciatic nerve was isolated, positioned on silver electrodes and stimulated for 20 secs (0.20 V, 0.5 ms, and 5 Hz). Arteriolar diameter was quantified using an automated video dimension analyzer. Contralateral SNS resulted in a 23.8%±3.9% increase in pial arteriolar diameter in the hindlimb sensory cortex under control conditions. Intravenous administration of caffeine at the lowest dose studied (5 mg/kg) had no effect on either resting arteriolar diameter or SNS-induced vasodilatation. However, at higher doses (10, 20, 30, and 40 mg/kg, intravenously), caffeine significantly (P<0.05; n=6) attenuated both resting diameter and cerebral blood flow (CBF) responses to somatosensory stimulation. Intravenous administration of theophylline (10, 20, and 40 mg/kg), another adenosine receptor antagonist, also significantly reduced SNS-induced vasodilatation in a dose-dependent manner. Hypercarbic vasodilatation was unaffected by either caffeine or theophylline. The results of the present study show that caffeine significantly reduces cerebrovascular responses to both adenosine and to somatosensory stimulation and supports a role of adenosine in the regulation of CBF during functional neuronal activity.