Ultrastructural study of brain microvessels in patients with traumatic cerebral contusions

Abstract

Brain tissue from 11 patients with traumatic cerebral contusions submitted to surgery was studied. Control biopsy specimens were obtained from 5 patients undergoing ventriculo-peritoneal shunts for "communicating" hydrocephalus. After collection, the small fragments were fixed by immersion in glutaraldehyde-osmium and embedded in Epon. Semi-thin sections stained with toluidine blue were observed with the light microscope. Thin sections stained with lead citrate and uranyl acetate were observed using a Jeol electron microscope. In tissues from patients with head trauma a clear space most probably corresponding to fluid accumulation was systematically observed around microvessels. Ultrastructurally endothelial cells from these specimens exhibited signs of marked intracellular oedema, tight junctions being intact. Pinocytotic activity was increased, mainly at the abluminal surface. Swelling of astrocytic perivascular processes and the appearance of macrophagic cells with voluminous lysosomes were also observed. The authors conclude that the oedema of endothelial cells probably represent a central fact in the pathophysiology of traumatic brain oedema and speculate on the putative involvement of stretch-activated receptors in this condition.

Blood-Brain Barrier Disruption Is an Early Event That May Persist for Many Years After Traumatic Brain Injury in Humans

“…As regards possible structural correlates of this acute BBB disruption, ultrastructural studies in animal models of TBI have identified a variety of alterations in vascular endothelia in the Page 14 of 22 acute phase following injury, including the formation of vacuoles, craters and microvilli (47,(57)(58)(59) some of which were later identified in human TBI (60,61). These very rapid changes in vascular structure and function have been attributed to a range of mechanisms such as direct perturbation of the vessels by mechanical forces, including the immediate disruption of vascular endothelial cells.…”

“…Additional, secondary insults following injury might also be detrimental to normal endothelial integrity and function, including acute rises in arterial pressure or intravascular thrombus formation (45,56,57). Finally, active physiological changes have also been described in both animals and humans following TBI, including increased transendothelial vesicular transport with otherwise intact tight junctions (47,59,61,62) as well as alterations to other components of the BBB, such as early astrocyte disruption and swelling (45,58).…”

Blood–Brain Barrier Pathophysiology in Traumatic Brain Injury

“…The post-traumatic increase in the permeability of the BBB to high-molecular-weight molecules could result from increased paracellular permeability of endothelial barrier associated with changes in expression, distribution, and/or function of tight junction proteins, and from augmented transport of pinocytotic vesicles across the BBB. There is evidence for increased pinocytotic activity in the cerebrovascular endothelium of TBI patients [50, 51]; however, the results from experiments in animal models of cerebral ischemic injury [52] raise the question about the quantitative importance of this pathophysiological process. Additional studies of post-traumatic changes in the permeability of the BBB to inert, low-molecular-weight markers would provide a better insight into the mechanisms underlying the opening of the BBB occurring after TBI.…”

“…By comparison, cytotoxic or cellular edema is associated with changes in cell metabolism and malfunction of membrane-associated pumps and ion transporters, which result in the cellular accumulation of osmotically active molecules and water. Among brain parenchymal cells, both the cerebrovascular endothelium and astrocytes appear to be most affected by post-traumatic cytotoxic edema [51], the features of which closely resemble those of cytotoxic edema observed after cerebral ischemia [53]. In the controlled cortical impact model of TBI in rats, the histological features of cytotoxic edema are apparent as early as 2–4 hours after injury (Szmydynger-Chodobska and Chodobski, unpublished observations).…”

“…Being located at the BBB, both NKCC1 and NHE1/2 may play a part in the formation of post-traumatic vasogenic edema by functioning in vectorial transport of Na + from the blood into the CNS [206]. NKCC1 and NHE1 are also the major regulators of the cell volume [206], and may therefore play important roles in promoting post-traumatic swelling of brain endothelium [51]. The pharmacological inhibition of activity of NKCC1 in rat models of TBI and cerebral ischemia was found to significantly reduce the formation of brain edema and decrease the extent of post-traumatic and post-ischemic loss of neural tissue [204, 207].…”