Frequency dependence of local cerebral blood flow induced by somatosensory hind paw stimulation in rat under normo- and hypercapnia.

We measured the field potential and the changes in local cerebral blood flow (LCBF) response during somatosensory activation (evoked LCBF) in alpha-chloralose--anesthetized rats by laser-Doppler flowmetry under normocapnia (PaCO(2)=34.3+/-3.8 mmHg) and hypercapnia (PaCO(2)=70.1+/-9.8 mmHg). Somatosensory activation was induced by electrical stimulation (0.2, 1, and 5 Hz with 1.5 mA for 5 s) of the hind paw. The neuronal activity of the somatosensory area of the hind paw was linear to the stimulus frequency, and there was no significant difference in the neuronal activity between hypercapnia and normocapnia. The baseline level of LCBF under hypercapnia was about 72.2% higher than that under normocapnia (p<0.01). The absolute response magnitude under hypercapnia was greater than that under normocapnia (p<0.05). The evoked LCBF under both conditions showed a frequency-dependent increase in the 0.2 to 5 Hz range, and the difference in the absolute response magnitude at the same stimulus frequency between normocapnia and hypercapnia became large with increasing stimulus frequency (p<0.05). On the other hand, after normalization to each baseline level there was no significant difference in the response magnitude of the normalized evoked LCBF between normocapnia and hypercapnia, indicating that the normalized evoked LCBF reflects neuronal activity even when the baseline LCBF was changed by the PaCO(2) level. The peak time and termination time of LCBF response curves with respect to the graded neuronal activity at 1 and 5 Hz stimulation increased significantly under hypercapnia, compared with those under normocapnia (p<0.05), although the rise time of 0.5 s was nearly constant. In conclusion, the results suggest a synergistic effect of the combined application of graded neuronal stimuli and hypercapnia on the LCBF response.

[1]  A Villringer,et al.  Coupling of cerebral blood flow to neuronal activation: role of adenosine and nitric oxide. , 1994, The American journal of physiology.

[2]  M. Purves,et al.  Control of cerebral blood vessels: Present state of the art , 1978, Annals of neurology.

[3]  P. Klatt,et al.  Ca2+/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide synthase. , 1992, The Biochemical journal.

[4]  E. Stein,et al.  Blood flow increases linearly in rat somatosensory cortex with increased whisker movement frequency , 1998, Brain Research.

[5]  I Kanno,et al.  Modulation of evoked cerebral blood flow under excessive blood supply and hyperoxic conditions. , 2000, The Japanese journal of physiology.

[6]  M. Raichle,et al.  Stimulus rate determines regional brain blood flow in striate cortex , 1985, Annals of neurology.

[7]  B. Siesjö,et al.  Cerebral circulation and metabolism. , 1984, Journal of neurosurgery.

[8]  C. Sobey,et al.  Journal of Cerebral Blood Flow and Metabolism Role of Potassium Channels in Regulation of Cerebral Vascular Tone , 2022 .

[9]  U. Dirnagl,et al.  Laser-Doppler measurements of concentration and velocity of moving blood cells in rat cerebral circulation. , 1997, Acta physiologica Scandinavica.

[10]  R. Albrecht,et al.  Role of nitric oxide, adenosine,N-methyl-d-aspartate receptors, and neuronal activation in hypoxia-induced pial arteriolar dilation in rats , 1995, Brain Research.

[11]  J. Phillis,et al.  Hypercapnia-induced increases in cerebral blood flow: roles of adenosine, nitric oxide and cortical arousal , 1997, Brain Research.

[12]  R L Haberl,et al.  Laser-Doppler assessment of brain microcirculation: effect of systemic alterations. , 1989, The American journal of physiology.

[13]  H. Kontos,et al.  Responses of cerebral arterioles to increased venous pressure. , 1982, The American journal of physiology.

[14]  L. Sokoloff,et al.  Relationships among local functional activity, energy metabolism, and blood flow in the central nervous system. , 1981, Federation proceedings.

[15]  X. Xu,et al.  SIN-1 reverses attenuation of hypercapnic cerebrovasodilation by nitric oxide synthase inhibitors. , 1994, The American journal of physiology.

[16]  A Villringer,et al.  Coupling of brain activity and cerebral blood flow: basis of functional neuroimaging. , 1995, Cerebrovascular and brain metabolism reviews.

[17]  Peter J. Goadsby,et al.  Cerebral blood flow is not coupled to neuronal activity during stimulation of the facial nerve vasodilator system , 1994, Brain Research.

[18]  John A Detre,et al.  Signal averaged laser Doppler measurements of activation–flow coupling in the rat forepaw somatosensory cortex , 1998, Brain Research.

[19]  I Kanno,et al.  CBF change evoked by somatosensory activation measured by laser-Doppler flowmetry: independent evaluation of RBC velocity and RBC concentration. , 1999, The Japanese journal of physiology.

[20]  L. D'alecy Sympathetic Cerebral Vasoconstriction Blocked by Adrenergic Alpha Receptor Antagonists , 1973, Stroke.

[21]  A Villringer,et al.  Nitric Oxide Modulates the CBF Response to Increased Extracellular Potassium , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  L. Edvinsson,et al.  Are brain vessels innervated also by central (non-sympathetic) adrenergic neurones? , 1973, Brain research.

[23]  M. Ueki,et al.  Functional Activation of Cerebral Blood Flow and Metabolism before and after Global Ischemia of Rat Brain , 1988, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  I. Kanno,et al.  Uncoupling of absolute CBF to neural activity. , 1997, Advances in experimental medicine and biology.

[25]  E. Gellhorn On the physiological action of carbon dioxide on cortex and hypothalamus. , 1953, Electroencephalography and clinical neurophysiology.

[26]  Gert E. Nilsson,et al.  Evaluation of a Laser Doppler Flowmeter for Measurement of Tissue Blood Flow , 1980, IEEE Transactions on Biomedical Engineering.

[27]  S. Snyder,et al.  Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[28]  K. Hossmann,et al.  Simultaneous measurements of microflow and evoked potentials in the somatomotor cortex of the cat brain during specific sensory activation , 1979, Pflügers Archiv.

[29]  B. Conrad,et al.  Dynamics of regional cerebral blood flow for various visual stimuli , 2004, Experimental Brain Research.

[30]  B. Bishop,et al.  Comparative influence of proprioceptors and chemoreceptors in the control of respiratory muscles. , 1973, Acta neurobiologiae experimentalis.

[31]  I Kanno,et al.  Hemodynamics evoked by microelectrical direct stimulation in rat somatosensory cortex. , 1999, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[32]  A. Ngai,et al.  Simultaneous Measurements of Pial Arteriolar Diameter and Laser-Doppler Flow during Somatosensory Stimulation , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[33]  Iwao Kanno,et al.  Evoked local cerebral blood flow induced by somatosensory stimulation is proportional to the baseline flow , 2000, Neuroscience Research.