Neuroscience
Assistant
Professor of Neuroscience. M.D.1997, First Moscow Medical Institute; Ph.D.
1980, Institute of Normal Physiology, Moscow.
Central Neural Regulation Of
Cerebral Blood Flow (Cbf)
Functional activation of central
neurons is accompanied by increase in glucose and oxygen utilization.
To provide the adequate level of both blood supply to the appropriate
area of brain increases. Special system exists within the brain that
maintains blood supply at the level sufficient for neurons to function
normally. Electrical or chemical stimulation of rostroventrolateral
medulla (RVL), which is an important part of brain blood flow regulatory
system, globally increases CBF without parallel changes of regional
glucose utilization. This area also plays an important role in hypoxic
cerebral vasodilation which is to the great extent reflexive as we demonstrated
recently. Vasodilatory pathways originating in the medulla ascend
through the thalamic area to the cerebral cortex. In the cerebral cortex
we discovered population of vasodilatory neurons which when excited
increase local cerebral blood flow. Most of the aspects of functioning
mechanisms of brain blood flow regulatory system are unknown. We
are characterizing different sides of the system by: (a) determining
the topographical representation within RVL of neurons initiating
cortical vasodilation; (b) identifying the subcortical nuclei innervated
by RVL whose cortical projections mediate the elevations in rCBF;
(c) identifying the intracortical neurons innervated by the subcortical
vasodilator pathway, whose excitation transduces an afferent neuronal
signal into vasodilation.
The long term objectives of
our studies are: First, to understand how the brain can protect itself
from hypoxia and/or ischemia by increasing perfusion through activation
of neural pathways. Our demonstration that the RVL is critical for
the cerebrovascular as well as systemic circulatory adjustments to
hypoxia may be critical not only to hypoxic stress but may protect
the brain in stroke and trauma. The discovery of a class of cortical
interneurons mediating neurogenic vasodilation could be of importance
not only in their capacity to match rCBF to metabolic need but also
by predicting that abnormalities of this network might lead, over time,
to a mismatch between metabolic demand and blood flow. Such a defect
might lead to cerebral pathology conceivably relating to multi-infarct
disease.
Second, the studies are highly
relevant to an understanding of the neural mechanisms underlying the
activation of rCBF in response to physiological and mental stimuli. Most
of the imaging methodologies, particular fast MRI (fMRI) and often
PET use rCBF as an index of neural events, yet still very little
is understood how the vascular signal is generated. For example selective
abnormalities in putative cortical vasodilator neurons might result
in failure of vascular signals to be generated even though neuronal
activation is normal. These studies would be the most detailed yet in charting
the functional neuroanatomy of a physiologically relevant vasodilator
network in brain.
Third, data may yield new important
insights in such still unknown phenomena as fainting, coma and regulation
of cerebral activity and hence mood, cognition and behavior.
Recent
Publications
Golanov,
E.V., Christensen, J.D. and Reis, D.J. The medullary cerebrovascular
vasodilator area (MCVA ) mediates cerebrovascular vasodilation and EEG
synchronization elicited from cerebellar fastigial nucleus in SpragueDawley
rats. Neurosci. Lett. 288: 183-186, 2000.
Glickstein,
S.B., Golanov, E.V. and Reis, D.J. Intrinsic neurons of fastigial
nucleus mediate neurogenic neuroprotection against excitotoxic and ischemic
neuronal injury in rat. J. Neurosci. 19: 4142-4154, 1999.
Golanov,
E.V., Christensen, J.D. and Reis, D.J. Role of potassium channels
in the central neurogenic neuroprotection elicited by cerebellar stimulation
in rat. Brain Res. 842: 496-500, 1999.
Golanov,
E.V. and Reis, D.J. A role for K-ATP-channels in mediating the elevations
of cerebral blood flow and arterial pressure by hypoxic stimulation of
oxygen-sensitive neurons of rostral ventrolateral medulla. Brain
Res. 827: 210-214, 1999.
Golanov,
E.V., Liu, F., and Reis, D.J. Stimulation of cerebellum protects hippocampal
neurons from global ischemia. Neuroreport 9: 819-824, 1998.
