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Christoph Leithner

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3 papers
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3

YNIMG Journal 2010 Journal Article

Elevating intracranial pressure reverses the decrease in deoxygenated hemoglobin and abolishes the post-stimulus overshoot upon somatosensory activation in rats

  • Martina Füchtemeier
  • Christoph Leithner
  • Nikolas Offenhauser
  • Marco Foddis
  • Matthias Kohl-Bareis
  • Ulrich Dirnagl
  • Ute Lindauer
  • Georg Royl

BOLD fMRI localizes activated brain areas by measuring decreases of deoxygenated hemoglobin (deoxy-Hb) caused by neurovascular coupling. To date, it is unclear whether intracranial pressure (ICP) modifies deoxy-Hb signaling for brain mapping. In addition, ICP elevation can test whether the BOLD post-stimulus undershoot, a transient hypo-oxygenation following functional activation, is due to vascular compliance rather than elevated cerebral metabolic rate of oxygen (CMRO2). We addressed these questions by studying the effect of ICP elevation on neurovascular coupling. In anesthetized rats, a cranial window was implanted over the somatosensory cortex. Using laser Doppler flowmetry and optical spectroscopy, changes in cerebral blood flow (CBF), cerebral blood volume (CBV) and deoxy-Hb were measured during electrical forepaw stimulation. Neuronal activity was monitored by somatosensory evoked potentials. ICP was elevated by subarachnoideal and intracisternal infusion of artificial cerebrospinal fluid. ICP elevation did not abrogate neurovascular coupling. However, the concomitant deoxy-Hb decrease was reduced (ICP=14mmHg) and reversed (ICP=28mmHg). Therefore, the validity of BOLD fMRI has to be questioned during increased ICP. Moreover, the amplitude of the deoxy-Hb post-stimulus overshoot was reduced with ICP elevation. CMRO2 was not elevated during the post-stimulus response. Therefore, these data provide experimental evidence that the BOLD post-stimulus undershoot is a passive vascular phenomenon.

YNIMG Journal 2008 Journal Article

Hypothermia effects on neurovascular coupling and cerebral metabolic rate of oxygen

  • Georg Royl
  • Martina Füchtemeier
  • Christoph Leithner
  • Dirk Megow
  • Nikolas Offenhauser
  • Jens Steinbrink
  • Matthias Kohl-Bareis
  • Ulrich Dirnagl

Neuronal activation is accompanied by a local increase in cerebral blood flow (CBF) and in cerebral metabolic rate of oxygen (CMRO2), caused by neurovascular and neurometabolic coupling. Hypothermia is used as a neuroprotective approach in surgical patients and therapeutically after cardiac arrest or stroke. The effect of hypothermia on neurovascular coupling is of interest for evaluating brain function in these patients, but has not been determined so far. It is not clear whether functional hyperaemia actually operates at subnormal temperatures. In addition, decreasing brain temperature reduces spontaneous CMRO2 following a known quantitative relationship (Q 10). Q 10 determination may serve to validate a recently introduced CMRO2 measurement approach relying on optical measurements of CBF and hemoglobin concentration. We applied this method to investigate hypothermia in a functional study of the somatosensory cortex. Anesthetized Wistar rats underwent surgical implantation of a closed cranial window. Using laser Doppler flowmetry and optical spectroscopy, relative changes in CBF and hemoglobin concentration were measured continuously. At the same time, an electroencephalogram (EEG) was recorded from the measurement site. By the application of ice packs, whole-body hypothermia was induced, followed by rewarming. Spontaneous EEG, CBF and CMRO2 were measured, interleaved by blocks of electrical forepaw stimulation. The Q 10 obtained from spontaneous CMRO2 changes of 4. 4 (95% confidence interval 3. 7–5. 1) was close to published values, indicating the reliability of the CMRO2 measurement. Lowering brain temperature decreased functional changes of CBF and CMRO2 as well as amplitudes of somatosensory evoked potentials (SEP) to the same degree. In conclusion, neurovascular and neurometabolic coupling is preserved during hypothermia.

YNIMG Journal 2001 Journal Article

No Evidence for Early Decrease in Blood Oxygenation in Rat Whisker Cortex in Response to Functional Activation

  • Ute Lindauer
  • Georg Royl
  • Christoph Leithner
  • Marc Kühl
  • Lorenz Gold
  • Jörn Gethmann
  • Matthias Kohl-Bareis
  • Arno Villringer

Using optical methods through a closed cranial window over the rat primary sensory cortex in chloralose/urethane-anesthetized rats we evaluated the time course of oxygen delivery and consumption in response to a physiological stimulus (whisker deflection). Independent methodological approaches (optical imaging spectroscopy, single fiber spectroscopy, oxygen-dependent phosphorescence quenching) were applied to different modes of whisker deflection (single whisker, full whisker pad). Spectroscopic data were evaluated using different algorithms (constant pathlength, differential pathlength correction). We found that whisker deflection is accompanied by a significant increase of oxygenated hemoglobin (oxy-Hb), followed by an undershoot. An early increase in deoxygenated hemoglobin (deoxy-Hb) proceeded hyperoxygenation when spectroscopic data were analyzed by constant pathlength analysis. However, correcting for the wavelength dependence of photon pathlength in brain tissue (differential pathlength correction) completely eliminated the increase in deoxy-Hb. Oxygen-dependent phosphorescence quenching did not reproducibly detect early deoxygenation. Together with recent fMRI data, our results argue against significant early deoxygenation as a universal phenomenon in functionally activated mammalian brain. Interpreted with a diffusion-limited model of oxygen delivery to brain tissue our results are compatible with coupling between neuronal activity and cerebral blood flow throughout stimulation, as postulated 110 years ago by C. Roy and C. Sherrington (1890, J. Physiol. 11: 85–108).

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