Persistent Hyperglycemia Induced Demyelination
and Fibrosis in Sensory Ganglia of Albino Rats
Muhamed Faizal and Aijaz Ahmed Khan*
Department of Anatomy, Aligarh Muslim University, India
Submission: March 03, 2018; Published: May 25, 2018
*Corresponding author: Aijaz Ahmed Khan, Department of Anatomy, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India, Email: firstname.lastname@example.org
How to cite this article: Muhamed Faizal, Aijaz Ahmed Khan. Persistent Hyperglycemia Induced Demyelination and Fibrosis in Sensory Ganglia of Albino
Rats. Anatomy Physiol Biochem Int J: 2018; 5(1): 555655. DOI: 10.19080/APBIJ.2018.05.555655.
Hyperglycemia-induced neurotoxicity is believed to affect both neurons and glial cells. This study was aimed to assess the histopathological alteration in the Trigeminal Ganglion (TrG) of STZ-induced diabetic adult male albino rats. A total number of 12 adult albino rats of either sex were divided into age-matched control and six month diabetic group. After six month animals of both groups were euthanized with ether anesthesia and perfuse with Karnovsky fixative. TrG from both sides was dissected, processed and 5 μm thick sections were stained for collagen. Light microscopy showed that long standing hyperglycemia was associated with increasing occurrence of dark and dead neurons and excess quantity and more thickened collagen fibers in the peri-ganglionic as well as peri-neuronal capsule and along the nerve fibers. It was concluded that glucose toxicity not only induces neuronal death and demyelination but also excessive deposition of collagen which appear to constitute the contributing factors in the progression of diabetic peripheral neuropathy.
Glucose toxicity cause functional and structural disorders in both central and peripheral nervous systems. Lack of blood-brain and blood-nerve barriers, sensory neurons in the TrG are highly sensitive to oxidative stress in diabetes . Mitochondrial dysfunction may leads to neuronal apoptosis. In addition, micro environmental alterations in the sensory ganglia may cause transformation of neuronal phenotype, ion channel
alterations, and abnormal growth factor signaling . Its clinical manifestations include sensory alterations in the orofacial complex like trigeminal neuralgia . The aim of present study was to assess the effect of longstanding hyperglycemic state on sensory neurons, nerve fibres and supporting tissue of TrG which may possibly explain the clinical symptoms following STZ induced hyperglycemia (Figure 1).
Total numbers of 12 adult albino rats of either sex (Weight
~250gm) from central animal house, Aligarh Muslim University,
Aligarh were used in the present study (IAEC- D:No-9025/2014).
After one week rats were divided into two groups
(I) Non-diabetic healthy control, age-matched;
(II) 6M diabetic experimental group. Experimental diabetic
model was induced by streptozotocin (STZ) (60mg/kg,
aqueous sol., I. P., single dose) whereas age-matched control
group did not receive any active compound.
Diabetic rats maintained blood sugar level more than 250
mg/dl throughout the experiment. After six month, rats were
euthanized with ether and perfusion fixed with Karnovsky
fixative. Both fixed TrG was dissected out then process for
paraffin embedding. Five μm thick sections were stained with
Cresyle Violet (CV) and Picro Sirus with Luxol Fast Blue (PSR
with LFB) and observed under the light microscope.
In high power view, TrG of control group showed normal
distribution of well defined neurons and few collagen fibres
around the neurons, along the nerve fibers and capsule of TrG.
Approximately similar features were also found in 6M diabetic
group but the number and thickness of collagen fibers were
markedly increased around the neurons, along the nerve fibers
and between clusters of neurons and capsule of the ganglia. In
addition increased number of dark neurons with degenerative
changes was also noticeable. Myelin showed poor staining and
perineuronal spaces were more frequently associated with
neurons of 6M diabetic group.
Histopathological observations in the current study were
suggestive of neurotoxic and degenerative effects of glucose
on the sensory ganglion. Some researchers have shown myelin
sheath defect and perineuronal spaces in chronic hyperglycemia
. I was suggested that changes may be apoptotic due to
progression of hyperglycemia. Similar results were also found in
the 6M diabetic group of the current study. One study observed
that type I, II and III collagen are the fibrillar - interstitial collagens
and are responsible for fibrosis. One related study observed that
p38 mitogen-activated protein kinase, PKC-β, AGE and RAGE
interaction to be responsible for the increased expression of
TGF-β which contributes to the development of fibrosis [5,6]. In
the present study 6M hyperglycemic group, exhibit thickening
of collagen around the neurons and along the nerve fibers and
ganglionic capsule. In addition fibrosis was also seen around
the intra-ganglionic vessels. These histopathological findings
indicated that the prolonged hyperglycemia seems to promote
both vascular pathology and neurotoxicity which is correlated
very well with previous observations regarding link between
hyperglycemia and sensory neurons and collagen connective
tissues in sensory ganglion [4,7].
Prolonged hyperglycemia induces neuronal death,
demyelination and increase fibrosis in the trigeminal ganglion
which appears to be an important causative factor in the
development of diabetic neuropathy.