Biomedical Engineering Reference
In-Depth Information
interfacial impedance or by causing the death of the contact neuron. These
persistent challenges limit the ecacy of neuronal implants.
The damage begins at the moment of insertion, when the electrode is
implanted through the meninges, via a hole made in the dura mater, through
the arachnoid and the pia matter, en route to the brain parenchim, where the
vascular density is of about 160 capillaries per mm
2
. Vascular damage happens
immediately by tissue and fluid displacement, vessel rupture, severing and
dragging, and breaking of cell bodies. A brain edema is formed locally
by serum proteins and by infiltration of cells such as neutrophil granulocytes,
T-lymphocytes and blood-borne macrophages, generating an inflammatory
response at the site of insertion. The wound healing mechanism is subsequently
initialized through thrombin release, nitric oxide (NO) production generating
oxidative stress, cytokine release and activation of microglia, the first line of
defense. The microglia engage in phagocytic activity similar to the role of
macrophages in non-CNS tissues, engulfing and digesting the cellular debris
generated by the injury, the molecules released by the dying neurons and the
plasma constituents of the blood infiltrated by capillary ruptures. Astrocytes
(which account for 30-65% of the glial cells) play a key role in forming a
physical barrier around the inserted electrode, known as the glial scar which is,
from the implant perspective, the undesirable component because it raises the
interfacial impedance.
Chronic implantation renders the glial scar more compact and confined to
the electrode. The continuous presence of the implant induces the formation of
a sheath composed of reactive glial cells, probably due to the 'frustrated
phagocytosis' process: macrophages meeting a foreign object in the body start
secreting lytic enzymes after interrogating the object in order to degrade
it. If the object is too big or non-degradable, the macrophages fuse into
multinucleated giant cells and continue to secrete superoxide agents and free
radicals, increasing inflammation and therefore exacerbating the neuronal
damage. Moreover, the mechanical friction due to brain micromotion arising
from physiological processes such as vascular pulsatility, cardiac rhythm and
respiratory pressure, spontaneous movements of the head, etc. can slightly
displace the electrodes—compressing, extending or even tearing the adjacent
soft tissue. Astrocytes sense mechanical stress and translate it into chemical
reactions. Increase in intracellular free sodium and calcium, activation of
phospholipases, free radical formation and secretion of potent antigens are all
causing delayed neuron depolarization and transient neuronal dysfunction.
Since any exacerbation of glial scar formation impedes and compromises
the recording or stimulation stability of the electrode, strategies to minimize
the above responses to the invading electrode must be found. Inactivating or
blocking the cellular receptors at molecular level, as well as the local delivery of
antibodies, antagonists and anti-inflammatory agents to surpass the initial
acute stage of the inflammation and attenuate the cellular response, or releasing
neurotrophic factors to guide and sustain the nearby neurons might all
constitute molecular-level solutions in an attempt to modulate and optimize the
tissue-electrode interface.
5-10
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