This review showed that the cerebellum of sodium fluoride treated animals exhibited degenerative changes especially in Purkinje cell layer, while the molecular and granular layers were less affected Ultra-structurally, increased the nuclear membrane irregularity, dilated rough endoplasmic reticulum and vacuolated mitochondria of Purkinje cells were observed

Fluoride is a chemical element which is widely distributed in the environment. It is a natural component of the earth's crest and occurs in varying concentration in rocks, soil, water and air. It is present in several chemical forms either organic or inorganic, one of the commonest inorganic fluorides is sodium fluoride (NaF) [1]. The main source of fluoride is tap water [2]. Other sources were food and drugs. Food containing fluoride included sea food and bony meals, fluoride concentrates in bones of most mammals Also dark green vegetables as the tea plant accumulate fluoride from soil and water [3]. Drugs which contains fluoride were mainly dental gels, tooth pastes and mouth rinses[4]. Cooking in Teflon lined cookware also increase the concentration of fluoride in our daily foods prepared inside them [5]. Excess fluoride intake causes fluorosis which is a progressive degenerative disorder known by clinical manifestations in bones and teeth [6].
Aim of our study is collect Data about effect of NaF on cerebellum as apart of central nerves system.

General Information of Sodium Fluoride

It is soluble in water. It is noncombustible. It is corrosive to aluminum. It is used as an insecticide. It is also used to fluorinate water supplies, as a wood preservative, in cleaning compounds, manufacture of glass, and for many other uses [7].

Sodium Fluoride Toxicity

Fluorosis has become an endemic problem worldwide. Toxic effects of high fluoride intake are observed in soft tissue such as liver, kidney, cerebrum and cerebellum[8]. Long term intake of high levels of fluoride in human causes neurological complications such as paralysis of limbs, vertigo, and spasticity in extremities and impaired mental acuity [9].

Sodium Fluoride Toxicity in Reproductive System

There is a study was designed to study the effect of NaF exposure for different durations. Naresh Kumar found significant decrease in Sperm count, motility, progressive motility and weight of epididymis [Figure 1]. but no change in the testicular weight in adult rabbits treated by 20 mg/kg body weight NaF for 30 days was given by using a tube attached to a hypodermic needle , and when extend the period to 60 days he observed a significant decrease in all the parameters [10].

Figure 1: A photomicrograph of rabbits testis fed on NaF (20 mg/ kg) for 30 days showed a lack of differentiation and maturation of spermatocytes and infiltration in the interstitial area of the seminiferous tubules without mature spermatozoa in the lumens of the seminiferous tubules (H&E stain x 200).

Sodium Fluoride Toxicity in Digestive System 

We found from our reading one study speak about there is gastrointestinal toxicity diagnosis by Histopathological examination as erosion and necrosis of the duodenum surface mucosa with hemorrhages, necrosis of Brunner's gland, clumped submucosa, and hypertrophy of muscles in muscular mucosa from using of NaF and there result appear in Young rabbits weighing 400-600 g injected daily with 5 mg NaF/kg for 15 weeks and then sacrificed [11] [Figure 2].

Figure 2: A photomicrograph of mice liver exposed to 5 mg/L/kg NaF for 15 days showed cellular disarray, congestion, cellular degeneration, and cellular vacuoles (Hematoxylin and Eosin (H&E) stain X 200).

Sodium Fluoride Toxicity in Urinary System 

There is kidney toxicity appear by histopathological examination as necrosis in glomerulus, Convoluted tubules and Bowman’s capsule lumen [Figure 3]. when he used adult albino mice in de-ionized water 5 ppm of NaF for 15 days and then sacrificed [12].

Figure 3: A photomicrograph of mouse kidney exposed to 5ppm/ 15 days fluoride showed necrosis in glomerulus, degenerative changes in Bowman’s capsule and alterations in glomerulus’s tubular region (H&E stain X 200).

Sodium Fluoride Toxicity in Nervous System 

Sodium Fluoride Toxicity on Brain
Earlier studies evaluated the brain histology after NaF inhalation at 300 ppm for 6 hr/day, 5 days week for 13 weeks and found mild or no histological changes indicating that this treatment was reversible [13] [Figure 4].

Figure 4: A photomicrograph of rat brain exposed to 300 ppm sulfuryl fluoride for 13 weeks showed vacuoles in brain white tracts and neuropil of the caudate-putamen but without necrosis or neuronal destruction (H&E stain X 330).
Observed generalized congestion and hemorrhages in vital organs (i.e. liver, heart, kidney, spleen, lung and brain) of rats treated with (NaF). Lakshmi, Pratap and Reddya found oxidation effect in brain. The enzymes SOD, Glutathione S-transferases (GST), and catalase decreased significantly (p<0.01) in contrast to Xanthine oxidase (XOD) activity, which moderately increased. Succinate dehydrogenase (SDH), Lactate dehydrogenase (LDH), Alanine transaminase (ALT), aspartate aminotransferase (AAT), and Creatine phospho kinase (CPK) activities and membrane-bound enzymes, Sodium (Na+), Potassium (K+), Magnesium (Mg++ and Calcium (Ca++) Adenosin Tri phosphatase (ATPase) and Acetylcholine (AChE) were decreased significantly (p<0.01) in brain are affected by fluoride with (20 mg/kg/body weight) for 14 days in adult female mice[14,15,16].

Sodium Fluoride Toxicity in Spinal Cord
Doaa, Nour-Edien and others found affect (NaF) at a dose of 12 mg/kg/day, for four weeks orally by gastric intubation received in adult male albino rats affect the grey matter of spinal cord, the histopathological alteration detected by using light and electron microscopy. In H&E-stained sections, showed various degrees of neurodegeneration in both the ventral and dorsal horns. Many cells were shrunken with dark cytoplasm and loss of nuclear details. Some of these cells were surrounded by vacuolated neuropil. Other cells showed central chromatolysis “cytoplasmic hyalinization”. Few cells appeared as ghost-like cells. The neuropil of both the ventral and dorsal horns showed some areas of vacuolation and many abnormal blood vessels. Some of these blood vessels had distorted endothelium while others were dilated and congested. In silver-stained sections, showed many shrunken cells with dark cytoplasm and loss of nuclear details. The neuropil showed many areas of vacuolation. Also, some degenerated axons with segmental disruption of myeline were observed in the neuropil. In Toluidine blue (TB) stained sections, the cytoplasm of motor neurons showed a significant decrease of Nissl’s granules content (p<0.01) that appeared faint blue in color [17,18] [Figure 5].

Figure 5: A photomicrograph of adult male rat brain exposed to 12 mg/kg/day NaF, for four weeks showed apparent decrease of Nissl’s granules content (arrows) in the motor neurons that appeared faint blue in color (Toluidine blue,×400).
Sodium Fluoride Toxicity on Locomotor Behavior and Memory
Vanaja Paul and others found that effect of NaF on locomotor behavior is observed when they used NaF at 20 mg/kg dose level daily for 60 days in adult female rats. The activities of total cholinesterase and acetylcholinesterase were determined in blood and brain regions, but no change was observed in the motor coordination and Acetylcholinesterase activity in cerebral cortex, brain stem and cerebellum of these animals. A cholinergic mechanism through a change in the activity of acetylcholinesterase may not account for this effect, since NaF treatment did not alter the activity this enzyme in brain regions [19]. 
Sodium Fluoride Toxicity on Cerebellum
The present review described the alterations in the histological structure of rat cerebellar cortex resulting from administration of NaF. Reported that any lesion to the cerebellar cortex was manifested in some animals as muscle weakness, tremors, loss of equilibrium, gait disturbance and hind limbs paralysis. Histological structure of the cerebellar cortex was disrupted, particularly the Purkinje cell layer that was the most affected cell population, while the molecular and granular layers were less affected [9].
 These results are similar to Omayma who found histological changes occurring in the cerebellar cortex, her result showed severe degenerative changes especially in Purkinje cells. There was multilayer disposition of these cells associated with structural changes in the form of dilated Rough endoplasmic reticulum (RER) and Golgi complex, swollen mitochondria in addition to marginated nuclear chromatin. The surrounding neuropil appeared vacuolated with accumulation of neuroglial cells. Many myelinated nerve fibers displayed disruption in myelination and irregular neurofilaments. On the other side, these result appear in 10 mg/kg NaF orally once daily for three months in adult male albino rats [20]. The results of [21,22] found that rabbits treated by NaF at 30 and 60 days these changes lead to paralysis of limbs and the histopathological alterations showed necrosis of Purkinje cells and edema with necrosis in the granular cell layer. The Purkinje cells of brains and cerebellar cortex showed degenerative changes in the form of loss of their characteristic pyriform shap, pyknotic or karyolitic nuclei, vacuolated cytoplasm and loss of many Purkinje cells in some areas [Figure 6-9].

Figure 6: A photomicrograph of a section in the cerebellar cortex of a 10 mg/kg NaF once daily for three months rat showed severely affected area with disappearance of many Purkinje cells. Notice, few shrunken irregular and scattered Purkinje cells (P) surrounded with vacuolated neuropil.

Figure 7: A photomicrograph of adult male rat cerebellar cortex exposed to 10 mg/kg NaF once daily for three months showed few shrunken irregular and scattered Purkinje cells (P) surrounded with vacuolated neuropil. H&E X 400.

Figure 8: A photomicrograph of adult male rat cerebellar cortex exposed to 10 mg/kg NaF once daily for three months showed Purkinje cells with absence of Nissels granules. The surrounding neuropil is vacuolated and many neuroglial cells (→) accumulate around Purkinje cells. H&E x 1000