Decreased cerebral blood flow and hemodynamic parameters during acute hyperglycemia in mice model observed by dual‐wavelength speckle imaging

Abstract

In this study, we use dual-wavelength optical imaging-based laser speckle technique to assess cerebral blood flow and metabolic parameters in a mouse model of acute hyperglycemia (high blood glucose). The effect of acute glucose levels on physiological processes has been extensively described in multiple organ systems such as retina, kidney, and others. We postulated that hyperglycemia also alters brain function, which in turn can be monitored optically using dual-wavelength laser speckle imaging (DW-LSI) platform. DW-LSI is a wide-field, noncontact optical imaging modality that integrates the principles of laser flowmetry and oximetry to obtain macroscopic information such as hemoglobin concentration and blood flow. A total of eight mice (C57/BL6) were used, randomized into two groups of normoglycemia (control, n = 3) and hyperglycemia (n = 5). Hyperglycemia was induced by intraperitoneal injection of a commonly used anesthetic drug combining ketamine and xylazine (KX combo). We found that this KX combo increases blood glucose (BG) levels from 150 to 350 mg/dL, approximately, when measured 18 minutes post-administration. BG continues to increase throughout the test period, with BG reaching an average of 463 ± 20.34 mg/dL within 60 minutes. BG levels were measured every 10 minutes from tail blood using commercially available glucometer. Experimental results demonstrated reductions in cerebral blood flow (CBF) by 55%, tissue oxygen saturation (SO 2 ) by 15%, and cerebral metabolic rate of oxygen (CMRO 2 ) by 75% following acute hyperglycemia. The observed decrease in these parameters was consistent with results reported in the literature, measured by a variety of experimental techniques. Measurements with laser Doppler flowmetry (LDF) were also performed which confirmed a reduction in CBF following acute hyperglycemia. In summary, our findings indicate that acute hyperglycemia modified brain hemodynamic response and induced significant David Shemesh and Naor Bokovza contributed equally to this work.

Short‐term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross‐over trial

“…Adults with obesity are at increased risk of cerebrovascular disease and neurological impairment. Acute and chronic hyperglycaemia impairs systemic vascular function (Piconi et al 2004;Ceriello et al 2008;Shemesh et al 2019) and contributes to development of vascular disease (Ceriello et al 2008;Habas & Shang, 2018). We hypothesized that ketone supplementation would confer benefit on the cerebrovasculature via the direct effects of β-OHB on cerebral metabolism and CBF (Hasselbalch et al 1996;Mikkelsen et al 2015;Svart et al 2018), as well as indirectly through its glucose-lowering effects (Neptune, 1956;Myette-Côté et al 2018Walsh et al 2021).…”

Alterations of Cerebral Blood Flow and Its Connectivity in Olfactory-Related Brain Regions of Type 2 Diabetes Mellitus Patients

“…The brain relies on the continuous supply of glucose as its main source of energy and metabolism, and changes in blood glucose concentrations directly affect brain function. Previous studies have shown that acute or chronic hyperglycemia is accompanied by reduced CBF ( Shemesh et al, 2019 ). The regional cerebral cortex is hypoperfused in T2DM patients, and chronic hyperglycemia disrupts the blood–brain barrier, leading to permanent brain cell damage, which demonstrates that altered cerebral hemodynamics is a potential mechanism of cognitive decline in T2DM patients ( Jansen et al, 2016 ).…”

Cerebral oxygenation and cardiac output responses during short repeated-sprints exercise and modulatory effect of glucose ingestion

“…In this experiment, we exploratory investigated the role of glucose ingestion and acute hyperglycaemia on the response of cerebral haemoglobin to sprint exercise. Although the brain almost exclusively relies on glucose for its metabolism and brain’s glucose uptake increases during exercise, hyperglycaemia has been shown to decrease the cerebral metabolic rate of oxygen (Ishibashi et al, 2016; Shemesh et al, 2019) and brain connectivity (Ishibashi et al, 2018) in healthy young participants. Acute and chronic hyperglycaemia also decreases CBF (Duckrow et al, 1985; Shemesh et al, 2019).…”

“…Although the brain almost exclusively relies on glucose for its metabolism and brain’s glucose uptake increases during exercise, hyperglycaemia has been shown to decrease the cerebral metabolic rate of oxygen (Ishibashi et al, 2016; Shemesh et al, 2019) and brain connectivity (Ishibashi et al, 2018) in healthy young participants. Acute and chronic hyperglycaemia also decreases CBF (Duckrow et al, 1985; Shemesh et al, 2019). In our experiment, glucose ingestion did not alter O 2 Hb and HHb responses to the repeated sprints exercise, although improving performance.…”