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Synchronization between cerebral and peripheral circulation at the pre-stroke stage is discussed in newborn rats using a model of stress-induced hemorrhagic stroke. It is considered how the degree of coherence between the rhythmic components of the blood flow velocity is varied under normal and pathological conditions. It is shown that the degree of entrainment changes significantly after severe stress, provoking the transformation of normal vascular dynamics into pathological ones. Strong increase in the coherence measure is revealed, characterizing the entrainment in the dynamics of blood flow in the microvascular network surrounding the sagittal sinus and in the vein of the neck. Such changes can be considered as a precursor of the latent stage of stroke development in risk groups.

Although many studies have indicated that electroacupuncture (EA) provides a neuroprotective effect against ischemic brain damage, the protective mechanism is not fully understood. Glutamate release and hippocampal blood flow in ischemia with EA were investigated to elucidate the neuroprotective mechanism of EA. Transient 5-minute ischemia was induced in gerbils. EA (7 Hz, 6 mA, for 30 minutes) delivered to the points called Fengfu (GV16) and Shendao (GV11) was administered pre-, intra- or post-ischemia. The procedure rescued hippocampal neurons from ischemic insult and significantly attenuated both ischemia-induced glutamate release and transient increase of cerebral blood flow (CBF) during reperfusion (hyperemia). Hyperemia as well as excessive glutamate after ischemia are regarded as important factors in brain damage as they lead to reperfusion injury. These results suggest that EA protects neurons by suppressing both glutamate release and reperfusion injury after ischemia.

The effect of moxibustion stimulation of various skin areas (cheek, forepaw, upper arm, chest, back, lower leg, hindpaw and perineum) on cerebral blood flow (CBF) of the parietal cortex was examined in anesthetized rats after eliminating emotional influences. Moxibustion stimulation was performed by burning a moxa cone of about 4 mg weight placed on the shaved skin. CBF of the parietal cortex was measured using a laser Doppler flowmeter. Stimulation of the cheek, forepaw, upper arm and hindpaw produced significant increases in CBF, but stimulation of the other areas did not produce significant responses. Moxibustion stimulation of the forepaw and hindpaw produced an increase in the mean arterial pressure (MAP), while stimulation of the other areas did not. After spinal transection at the 2nd thoracic level, the MAP response to stimulation of the forepaw was abolished, whereas the CBF response to stimulation of the forepaw remained. The CBF response in spinalized rats was not affected by cutting cervical sympathetic and facial parasympathetic nerves, while it was almost abolished by intravenous administration of muscarinic and nicotinic cholinergic blocking agents. The CBF response was abolished by crushing the brachial plexus ipsilateral to the stimulated side. It is suggested that the increase in CBF, independent of MAP and emotional responses, elicited by moxibustion stimulation is a reflex response whose afferent pathway is composed of somatic afferent nerves, and whose efferent pathway involves intracerebral cholinergic nerves. A contribution of endogenous opioids in the present CBF responses was neglected, because naloxone did not influence the CBF responses.

Electroacupuncture (EA) is widely used to treat disorders of the nervous system, such as stroke. The aim of the present study was to investigate the effect of EA on cerebral blood flow (CBF) in cerebral ischemic rats. We developed an animal model of cerebral ischemia (CI) by occluding the blood flow of both common carotid arteries in Sprague-Dawley (SD) rats; 2 or 15 Hz EA was applied to both Zusanli acupoints. The levels of nitric oxide (NO) in the peripheral blood and amounts of calcitonin gene-related peptide (CGRP) in the cerebral cortex and thalamus were measured. In addition, L-N (G)-nitro arginine methyl ester (L-NAME) was used to measure the changes in CBF induced by EA in rats with and without CI. The results indicated that both 2 and 15 Hz EA increase the mean CBF in rats with and without CI. However, neither 2 nor 15 Hz EA induced changes in levels of NO in peripheral blood or changes in CGRP levels in cerebral cortex and thalamus. In addition, L-NAME did not change the increase in CBF. We concluded that both 2 and 15 Hz EA at both Zusanli acupoints induced the increase of CBF in rats with and without CI. Whether the effect of EA is related to NO or CGRP will be investigated in a future study.

In this study, numerical simulations are performed to analyze the brain temperature reduction in swine during selective head cooling, whole body cooling or while the animals experience ischemia. Brain temperature is calculated using a time dependent thermal model that incorporates available experimental measurements of the rectal temperature, the cerebral blood flow and the cerebral metabolic rate of oxygen consumption.

The calculated temperature distribution is validated against the in vivo temperature measurements recorded during the different experiments. These comparisons help to better understand the relations between brain temperature, blood flow and metabolic activity, which are essential to successfully apply hypothermia in the treatment of brain injury.

The calculations presented here reproduce the temperature behavior observed in all the experiments considered. It is observed that the arterial temperature and the cerebral metabolic rate are important parameters that affect the deep tissue temperature. It is also concluded that the accurate knowledge of parameters such as the skin and bone thermal conductivity are necessary for effective modeling.

This paper analyzes the effect of different cooling and rewarming strategies on the brain temperature distribution before and after circulatory arrest in adults and children. The temperature variations during systemic cooling, circulatory arrest, and rewarming are calculated using a thermal model that incorporates physiological parameters. The calculations presented here explain why sometimes hypothermia does not show the expected neuroprotective effect.

This work shows the importance of departing from a steady temperature distribution when using deep hypothermic circulatory arrest. In the calculations, the external cooling conditions of the head are varied, and it is observed that hypothermic cardiopulmonary bypass (CPB) together with external head cooling help reduce the temperature gradients within the head during periods of reduced blood flow, and reduces the temperature increase in the deep tissue produced by the residual cerebral metabolic activity. The results presented here agree with previous experimental observations^1–3 regarding the duration of systemic cooling using CPB.

Focal ischemia due to reduction of cerebral blood flow (CBF), creates 2 zones of damage: the core area, which suffers severe damage, and penumbra area, which surrounds the core and suffers intermediate levels of injury. Objectives: A novel method is introduced, which evaluates mitochondrial function in the core and in the penumbra, during focal cerebral ischemia. Methods: Wistar rats underwent focal cerebral ischemia by middle cerebral artery occlusion (MCAO) for 60 minutes, followed by 60 minutes of reperfusion. Mitochondrial function was assessed by a unique Multi-Site – Multi-Parametric (MSMP) monitoring system, which measures mitochondrial NADH using fluorometric technique, and CBF using Laser Doppler Flowmetry (LDF). Results: At the onset of occlusion, CBF dropped and NADH increased significantly only in the right hemisphere. CBF levels were significantly lower and NADH significantly higher in the core than in the penumbra. After reperfusion, CBF and NADH recovered correspondingly to the intensity of ischemia. Conclusion: Application of the MSMP system can add significant information for the understanding of the cerebral metabolic state under ischemic conditions, with an emphasis on mitochondrial function.

The collateral circulation is crucial for the pathophysiology and outcome of acute cortical ischemia. Current understanding of collateral circulation still remains sparse, largely due to prior limitations of spatial or/and temporal resolution in methods to evaluate these diminutive redistributive routes of cerebral blood flow (CBF) especially in leptomeningeal anastomoses that connected cortical arteries. In the study, based on a mini-stroke model, laser speckle imaging with high spatiotemporal resolution was used to assess the dynamic evolution of the collateral circulation around a mini-ischemia in the rat cortex. We found that the blood flow and diameter in the intra-arterial anastomoses were enhanced immediately after the ligation of one branch of middle cerebral artery and recovered to baseline level as arterial recirculation was performed. Whereas the communicative flow-through of the posterior cerebral artery and the middle cerebral artery anastomoses was not significant enough to be determined. This is the evidence that intra-arterial anastomoses were the primary routes to restore blood flow into the ischemic territory during the acute phase of ischemia, and laser speckle imaging method was proven as a powerful tool to be potential for subserving further investigation of the collateral circulation.

The use of anesthetics is a well-known treatment for severely injured patients. In the present study we tested the pathophysiology of several levels of injury damage in a rat model and also tested the effect of Equithesin on brain vitality in these models. Traumatic Brain Injury (TBI) was induced using the fluid percussion injury model in four levels: mild, moderate and two levels of severe TBI. Brain real-time evaluation was performed by the multiparametric monitoring assembly (MPA) which enable cerebral blood flow (CBF) monitoring by laser Doppler flowmetry, mitochondrial NADH (Nicotinamide adenine dinucleotide) monitoring by the fluorometric technique, ionic homehostasis using special mini-electrodes, intracranial pressure (ICP) by the ICP camino device and needle electrodes for ECoG (Electrocorticogram) recording. Our results showed high correlation between the level of impact and the extent of changes in the physiological properties of the injury as indicated by the changes in all parameters monitored using the MPA device. Moreover, Equithesin improved CBF, ionic extracellular level and mitochondrial redox state following mild and moderate TBI while in severe TBI, Equithesin did not improve the metabolic state of the cerebral cortex, although it decreased the mortality rate from 66% to 20%, and following extra-severe TBI level, Equithesin did not improve survival rate. In conclusion it seems that Equithesin's protective effect exists under mild to moderate levels of injury and not in case of severe injuries.

A novel hemodynamic model has been recently introduced, which provides analytical relationships between the changes in cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO₂), and associated changes in the tissue concentrations of oxy- and deoxy-hemoglobin (ΔO and ΔD) measured with near-infrared spectroscopy (NIRS) [S. Fantini, Neuroimage85, 202–221 (2014)]. This novel model can be applied to measurements of the amplitude and phase of induced hemodynamic oscillations as a function of the frequency of oscillation, realizing the novel technique of coherent hemodynamics spectroscopy (CHS) [S. Fantini, Neuroimage85, 202–221 (2014); M. L. Pierro et al., Neuroimage85, 222–233 (2014)]. In a previous work, we have demonstrated an in vivo application of CHS on human subjects during paced breathing [M. L. Pierro et al., Neuroimage85, 222–233 (2014)]. In this work, we present a new analysis of the collected data during paced breathing based on a slightly revised formulation of the hemodynamic model and an efficient fitting procedure. While we have initially treated all 12 model parameters as independent, we have found that, in this new implementation of CHS, the number of independent parameters is eight. In this article, we identify the eight independent model parameters and we show that our previous results are consistent with the new formulation, once the individual parameters of the earlier analysis are combined into the new set of independent parameters.

Hypoxia is closely related to many diseases and often leads to death. Early detection and identification of the hypoxia causes may help to promptly determine the right rescue plan and reduce the mortality. We proposed a new multiparametric monitoring method employing mitochondrial reduced nicotinamide adenine dinucleotide (NADH) fluorescence, regional reflectance, regional cerebral blood flow (CBF), electrocardiography (ECG), and respiration under six kinds of acute hypoxia in four categories to investigate a correlation between the parameter variances and the hypoxia causes. The variation patterns of the parameters were discussed, and the combination of NADH and CBF may contribute to the identification of the causes of hypoxia.

Using the laser speckle contrast imaging and wavelet-based analyses, we investigate a latent (a "hidden") stage of the development of intracranial hemorrhages (ICHs) in newborn rats. We apply two measures based on the continuous wavelet-transform of blood flow velocity in the sagittal sinus, namely, the spectral energy in distinct frequency ranges and a multiscality degree characterizing complexity of experimental data. We show that the wavelet-based multifractal formalism reveals changes in the cerebrovascular blood flow at the development of ICH.

Neonatal stroke is similar to the stroke that occurs in adults and produces a significant morbidity and long-term neurologic and cognitive deficits. There are important differences in the factors, clinical events and outcomes associated with the stroke in infants and adults. However, mechanisms underlying age differences in the stroke development remain largely unknown. Therefore, treatment guidelines for neonatal stroke must extrapolate from the adult data that is often not suitable for children. The new information about differences between neonatal and adult stroke is essential for identification of significant areas for future treatment and effective prevention of neonatal stroke. Here, we studied the development of stress-induced hemorrhagic stroke and possible mechanisms underlying these processes in newborn and adult rats. Using histological methods and magnetic resonance imaging, we found age differences in the type of intracranial hemorrhages. Newborn rats demonstrated small superficial bleedings in the cortex while adult rats had more severe deep bleedings in the cerebellum. Using Doppler optical coherent tomography, we found higher stress-reactivity of the sagittal sinus to deleterious effects of stress in newborn vs. adult rats suggesting that the cerebral veins are more vulnerable to negative stress factors in neonatal vs. adult brain in rats. However, adult but not newborn rats demonstrated the stroke-induced breakdown of blood brain barrier (BBB) permeability. The one of possible mechanisms underlying the higher resistance to stress-related stroke injures of cerebral vessels in newborn rats compared with adult animals is the greater expression of two main tight junction proteins of BBB (occludin and claudin-5) in neonatal vs. mature brain in rats.

Based on the laser speckle contrast imaging (LSCI) and the multiscale entropy (MSE), we study in this work the blood flow dynamics at the levels of cerebral veins and the surrounding network of microcerebral vessels. We discuss how the phenylephrine-related acute peripheral hypertension is reflected in the cerebral circulation and show that the observed changes are scale-dependent, and they are significantly more pronounced in microcerebral vessels, while the macrocerebral dynamics does not demonstrate authentic inter-group distinctions. We also consider the permeability of blood–brain barrier (BBB) and study its opening caused by sound exposure. We show that alterations associated with the BBB opening can be revealed by the analysis of blood flow at the level of macrocerebral vessels.