Extracellular Diffusion Parameters in the Rat Somatosensory Cortex during Recovery from Transient Global Ischemia/Hypoxia

Abstract

Changes in the extracellular space diffusion parameters during ischemia are well known, but information about changes during the postischemic period is lacking. Extracellular volume fraction (a) and tortuosity (k) were determined in the rat somatosensory cortex using the real-time iontophoretic method; diffusion-weighted magnetic resonance imaging was used to determine the apparent diffusion coefficient of water. Transient ischemia was induced by bilateral common carotid artery clamping for 10 or 15 mins and concomitant ventilation with 6% O 2 in N 2 . In both ischemia groups, a negative DC shift accompanied by increased potassium levels occurred after 1 to 2 mins of ischemia and recovered to preischemic values within 3 to 5 mins of reperfusion. During ischemia of 10 mins duration, a typically decreased to 0.07 ± 0.01, whereas k increased to 1.80 ± 0.02. In this group, normal values of a = 0.20±0.01 and k = 1.55±0.01 were registered within 5 to 10 mins of reperfusion. After 15 mins of ischemia, a increased within 40 to 50 mins of reperfusion to 0.29 ± 0.03 and remained at this level. Tortuosity (k) increased to 1.81±0.02 during ischemia, recovered within 5 to 10 mins of reperfusion, and was increased to 1.62 ± 0.01 at the end of the experiment. The observed changes can affect the diffusion of ions, neurotransmitters, metabolic substances, and drugs in the nervous system.

The effects of levosimendan on brain metabolism during initial recovery from global transient ischaemia/hypoxia

“…In the traumatic brain model injury model, a 100-fold higher concentration was required to achieve significant affects [15]. The low cerebral concentrations could be a consequence of the rapid redistribution of the levosimendan bolus [37] and the delayed disruption of the blood–brain barrier related to the insult [22,38], which appears to be a prerequisite to achieve higher levosimendan levels within the brain.…”

“…A previously established protocol was modified to investigate the effects of levosimendan on ischaemic brain injury [22]. Thirty male Wistar rats (Charles River, Sulzfeld, Germany, 300–350 g) were anaesthetised by an intraperitoneal injection of 1.5 g/kg urethane (Sigma-Aldrich Chemie GmbH, Steinheim, Germany).…”

Targeting ischemic penumbra Part II: selective drug delivery using liposome technologies

“…In such case, liposomes may mainly depend on endocytosis and transcellular route for drug delivery, similar to the mechanism that allows their passage through the BBB (Patel et al 2009). Because of the shrinkage of extracellular space (Thorne and Nicholson 2006; Zoremba et al 2008), relatively small-sized liposomes may facilitate interstitial diffusion in ischemic tissue; but a smaller size also increases the risk of potential pulmonary toxicity (Nel et al 2006). …”

Targeting ischemic penumbra Part II: selective drug delivery using liposome technologies

“…For example, the regional cerebral blood flow (rCBF) in the inner penumbra is only about 15 ml/100g/min (Murphy et al 2006;Ohashi et al 2005). Moreover, the extracellular space (ECS) is also decreased during ischemia (Thorne and Nicholson 2006;Zoremba et al 2008). Ischemia causes cytotoxic edema that increases cell volume by 12% and reduces ECS by 50%.…”

“…In such case, liposomes may mainly depend on endocytosis and transcellular route for drug delivery, similar to the me- chanism that allows their passage through the BBB (Patel et al 2009). Because of the shrinkage of extracellular space (Thorne and Nicholson 2006;Zoremba et al 2008), relatively small-sized liposomes may facilitate interstitial diffusion in ischemic tissue; but a smaller size also increases the risk of potential pulmonary toxicity (Nel et al 2006). …”